EP2105202A1 - Appareil et procédé pour mélangeur et pompe microfluide - Google Patents

Appareil et procédé pour mélangeur et pompe microfluide Download PDF

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Publication number
EP2105202A1
EP2105202A1 EP08153497A EP08153497A EP2105202A1 EP 2105202 A1 EP2105202 A1 EP 2105202A1 EP 08153497 A EP08153497 A EP 08153497A EP 08153497 A EP08153497 A EP 08153497A EP 2105202 A1 EP2105202 A1 EP 2105202A1
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EP
European Patent Office
Prior art keywords
magnetic field
rods
magnetic
mixing
channel
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.)
Ceased
Application number
EP08153497A
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German (de)
English (en)
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designation of the inventor has not yet been filed The
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Stichting Dutch Polymer Institute
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Stichting Dutch Polymer Institute
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Publication date
Application filed by Stichting Dutch Polymer Institute filed Critical Stichting Dutch Polymer Institute
Priority to EP08153497A priority Critical patent/EP2105202A1/fr
Priority to PCT/IB2009/051234 priority patent/WO2009118689A1/fr
Publication of EP2105202A1 publication Critical patent/EP2105202A1/fr
Ceased legal-status Critical Current

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Classifications

    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps
    • 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
    • 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
    • B01F33/45—Magnetic mixers; Mixers with magnetically driven stirrers
    • B01F33/452—Magnetic mixers; Mixers with magnetically driven stirrers using independent floating stirring elements

Definitions

  • the present invention relates to microfluidic systems. More particularly, the invention relates to an apparatus and a corresponding method for rapid mixing and pumping of fluids.
  • Micro-fluidics is the science and technology of manipulating and analyzing fluid flow in structures of sub-millimeter dimensions. This field is particularly relevant for the development of lab-on-chip devices, which can be pictured as credit-card-sized fluidic systems containing small channels and chambers, typically with sizes of 0.1 mm or less, in which processes such as pumping, mixing and routing of the liquids, and separation, reaction, and detection of individual components present in these liquids are integrated. In this way a complete large-scale analysis laboratory is miniaturized and combined on a single chip.
  • a special challenge in micro-fluidic systems is to create efficient mixing flows. Due to the small channel sizes, the Reynolds number is generally low and flows are non-turbulent. On the other hand, the channel size is often too large for molecular diffusion to be effective in mixing within a reasonable time. To obtain efficient mixing, special strategies must therefore be followed. An approach is to create repeatedly stretching and folding flow patterns, leading to so-called chaotic advection that causes effective mixing.
  • the existing micro-mixers can be divided into two general classes, namely passive and active micro-mixers. Passive micro-mixers do not require external energy, and the mixing process relies entirely on chaotic advection or diffusion. The effect is often achieved by special geometrical features like channel shape or corrugations on the channel walls.
  • Active micro-mixers use the disturbance generated by an external field for the mixing process, and thus they require external energy. Examples are: the application of sinusoidal pressure pulses to the micro-channel through the channel inlets, electro-hydrodynamic forcing using integrated electrodes, integrated micro-actuators that are elctrostatically actuated, and acoustic streaming. A particular approach is to use magnetic actuation to achieve active micro-mixing
  • US 2004/0114458 A1 discloses a device for mixing fluids having a mixing chamber, a ferromagnetic core at the center of the chamber, a magnetic field means around the perimeter of the chamber, and a number of paramagnetic beads in the chamber to mix any fluids that may be present.
  • the beads oscillate in a radial pattern around the ferromagnetic core, between the core and the magnetic field means, and thereby mix the fluids.
  • the device requires a ferromagnetic core in the center of the chamber.
  • the oscillating motion of the beads requires a complex control mechanism to compensate for different properties of the fluids to be mixed, in order to provide maximum mixing within the chamber. Further, such a system has no demonstrated efficacy as a pump mechanism.
  • the micro stir-bar is manufactured as a single piece with the channel via a multiple layer deposition process, and has a symmetric, fixed point of rotation within the channel.
  • the traditional monolithic construction described requires that the micro stir-bar is manufactured to very closely match the width of the fluid channels.
  • a 50 ⁇ m gap between the tip of the micro stir-bar and the inner wall of the channel was identified as being so large as to reduce mixing efficiency.
  • the author discloses how he was able to achieve a gap of only 10 ⁇ m, but even that small gap provides room for a laminar flow to avoid the micro stir-bar.
  • the author describes the alternative use of the micro stir-bar as a pump to move fluid within the channel. Similar to the mixer application, the pump application discloses that the single-piece micro stir-bar is manufactured together with the channel via a multiple layer deposition process so that the micro stir-bar is captured and has a fixed point of rotation within the channel. The disclosed methods of production are quite expensive and time-consuming, especially for a one-time-use device.
  • an apparatus for rapid mixing and pumping of fluids comprising: a movable and controllable rotating magnetic field; a micro fluidic channel including a mixing zone and a pumping chamber within said magnetic field; and a plurality of magnetic rods within said microfluidic channel and said magnetic field, whereby said rotating magnetic field applies torque to said magnetic rods.
  • the configuration of the apparatus may easily be varied from mixing to pumping and back to mixing simply by adjusting the focus of the rotating magnetic field.
  • the apparatus can be manufactured relatively cheaply.
  • multiple magnetic rods e.g. ferromagnetic, paramagnetic or super-paramagnetic rods
  • the magnetic rods due to their shape anisotropy, the magnetic rods have greater stability in a rotating magnetic field than colloid-stabilized aggregates.
  • the apparatus may include a means for moving the rotating magnetic field from the mixing zone to the pumping chamber to change the function of the device from a mixer to a pump.
  • the pumping chamber may be asymmetric to enhance the fluid movement.
  • Asymmetry in the geometry of the chamber enhances the pressure difference between the inlet and outlet of the device and improves the pumping characteristics.
  • Asymmetry can be created by placing the focus of the rotating magnetic field toward a side of the channel or by placing the inlet and outlet of the pumping chamber asymmetrically with respect to each other.
  • the inner surface of the microfluidic channel and/or the magnetic rods may include a non-stick coating, e.g., a polymer. This feature is helpful where the rods tend to stick to the walls of the channel, and will encourage more complete and rapid mixing and/or pumping by maximizing the number of rods in motion.
  • the rotating magnetic field may be provided by a rotating permanent magnet or by an electromagnet array.
  • the latter may consist of a set of electromagnets that are external to the micro-fluidic device, and that can be separately addressed. It may consist also of magnetic field generating means integrated in the micro-fluidic devices, such as integrated coils or integrated current wires.
  • the rotating permanent magnet provides a mechanical solution to the problem of a rotating magnetic field and provides a low-cost solution.
  • the electromagnetic array provides a space- and time-variable magnetic field that is electronically adjustable and with few, if any, any moving parts.
  • the magnetic rods may comprise a large aspect ratio to enhance the automatic and spontaneous formation, under a magnetic field, of enlongated assemblies of numerous rods, and thereby enhance mixing and pumping effectiveness and efficiency.
  • the magnetic rods may be manufactured by a templated electrodeposition process. Such a process may include the electrodeposition of Nickel (Ni) in a Whatman Anodisc membrane or a track etch membrane. Upon formation of the rods, the membrane may be etched away to yield a large number of uniform rods which may be suspended in water or another solution for injection into a microfluidic channel.
  • a templated electrodeposition process may include the electrodeposition of Nickel (Ni) in a Whatman Anodisc membrane or a track etch membrane.
  • the membrane may be etched away to yield a large number of uniform rods which may be suspended in water or another solution for injection into a microfluidic channel.
  • the microfluidic channel may include one or more fluid inlets and at least one fluid outlet. Multiple fluids may be introduced into the microfluidic channel in a controlled manner, each fluid having a separate inlet to reduce the likelihood of uncontrolled or unwanted mixing. Alternatively, one or more fluids or dry reagents may be stored in the chip, and released to be mixed with or dissolved in a fluid that is introduced in the channel through an inlet.
  • a method of micro fluidic mixing and pumping comprising the steps of: creating a movable and controllable rotating magnetic field around a microfluidic channel including a mixing zone and a pumping chamber; capturing a plurality of magnetic rods within said magnetic field and inside said microfluidic channel; moving said magnetic field to said mixing zone of said microfluidic channel; applying torque via said magnetic field to a plurality of magnetic rods within said mixing zone of said microfluidic channel to make said magnetic rods rotate; moving said magnetic field to said pumping chamber of said microfluidic channel to make said magnetic rods move to said pumping chamber; and applying torque via said magnetic field to said plurality of magnetic rods within said pumping chamber of said microfluidic channel to make said magnetic rods rotate.
  • Figs. 1a - 1b show plan views and Fig. 2 shows a perspective view, respectively, of a microfluidic mixing and pumping device 100 in accordance with embodiments of the present invention.
  • the microfluidic mixing and pumping device 100 includes a substrate 101, e.g., a chip, having a microfluidic channel 104 extending through it.
  • the microfluidic channel 104 includes a mixing zone 106 and a pumping chamber 108.
  • a movable and controllable rotating magnetic field 102 is established so as to include the mixing zone 106 or the pumping chamber 108 within said magnetic field 102.
  • a plurality of magnetic rods 116 are placed into the channel 104 and are influenced by the rotating magnetic field 102.
  • the microfluidic channel 104 may include one or more fluid inlets 110 so that two or more different fluids may be controllably delivered into the micro fluidic channel 104 for mixing and observation.
  • one or more fluids or dry reagents may be stored in the chip, and released to be mixed with or dissolved in a fluid that is introduced in the channel through an inlet.
  • the microfluidic channel 104 may include at least one fluid outlet 112, whereby the mixed fluid C may be pumped out of the channel 104.
  • An observation area 114 may be located along the microfluidic channel, to include the area between the mixing zone 106 and the pumping chamber 108.
  • the device 100 may include a means 105 for moving the rotating magnetic field 102 from the mixing zone 106 to the pumping chamber 108, or vice versa, whereby the device 100 may be changed from a mixer to a pump or from a pump to a mixer. Towards that end, the focus 103 of the rotating magnetic field 102 may be shifted from the mixing zone 106 to the pumping chamber 108.
  • the means 105 for moving the magnetic field may be electronic or mechanical in nature, or may be a combination of electronic and mechanical controls to properly direct the focus of the magnetic field 103 and thereby the magnetic rods 116 into the desired portion of the microfluidic channel 104. The magnetic rods 116 will move in the magnetic field gradient towards the heart of the rotating magnetic field 102.
  • the substrate 101 having the microfluidic channel 104 may be moved within a stationary rotating magnetic field 102 to move the focus 103 of the rotating magnetic field 102 from the mixing zone 106 to the pumping chamber 108.
  • the magnetic field 102 may be adjusted so that it may be strong enough to prevent the magnetic rods 116 from washing out when the fluids A, B, C flow and weak enough to enable rotation of the rods 116.
  • the rotating magnetic field 102 is created by a rotating permanent magnet.
  • the rotating magnetic field 102 may be established by a stationary or rotating electromagnet array.
  • the pumping chamber 108 may be constructed so as to be asymmetric to enhance the pumping efficiency.
  • the inner surface of the microfluidic channel 104 may include a non-stick coating to reduce any tendency of the magnetic rods 116 to stick to the channel 104.
  • the magnetic rods 116 may be manufactured so as to comprise a large length-to-diameter aspect ratio. In one embodiment, the magnetic rods 116 have a length of about 25 ⁇ m and a width of about 0.4 ⁇ m. The rods 116 may be manufactured in a number of very uniform sizes by a templated electrodeposition process. In one embodiment, the rods 116 are made of nickel (Ni) in a Whatman Anodisc membrane. After the membrane is etched away, the rods may be suspended in water or another fluid medium for injection into the microfluidic channel. The magnetic rods 116 may include a non-stick coating to prevent sticking to the wall of the channel 104.
  • a method of microfluidic mixing and pumping comprises the steps of:
  • the magnetic rods 116 Upon rotation of the magnetic field 102, e.g., at 300 rpm, the magnetic rods 116 will self-assemble and begin to rotate in unison with the rotating magnetic field 102. A number of individual rods may strike the walls of the microfluidic channel 104 and be displaced from the mass of rods, only to reassemble with the mass again. Thus, the magnetic rods 116 contact the walls of the microfluidic channel 104 and destroy any laminar flow that may cling to the walls of the microfluidic channel 104. Observation of the magnetic rods 116 in motion reveals that numerous vortices are created and visible in the fluid flow just after the magnetic rods 116. Further, the use of multiple magnetic rods 116 provides more effective mixing and pumping than a single impeller.
  • Figs. 3a - 3c show respective plan and perspective views of embodiments of a pumping chamber 108 for a microfluidic mixing and pumping device 100 in accordance with an embodiment of the present invention.
  • the pumping chamber 108 may be asymmetric to enhance pumping efficiency. This asymmetry can take many forms, as shown in Figs. 3a-3c .
  • a focus point 103 may be designated for the approximate center of the rotating magnetic field 102, whereby the rotation of the magnetic rods 116 may be made more uniform. Uniformity of the rotation of the magnetic rods 116 may enhance the efficiency of the pumping chamber 108.
  • the pumping process may begin when the magnetic rods 116 are moved into the pumping chamber 108.
  • the plurality of magnetic rods 116 is rotated within the pumping chamber 108 at about 100 to over 1000 revolutions per minute, under the influence of the rotating magnetic field 102.
  • the plurality of magnetic rods 116 are rotated together to move and displace the fluids and thereby pump the fluids. There may be a certain amount of relative motion between individual magnetic rods 116, but they continue to rotate together under the influence of the rotating magnetic field 102.
  • Fig. 3a shows a plan view of a linear and planar microfluidic channel 104 that is attached tangentially to the pumping chamber 108.
  • Fig. 3b shows a plan view of a pumping chamber 108 that is attached between two segments of microfluidic channel 104 which are planar along only one axis. Only one segment of the channel 104 is attached tangentially to the pumping chamber 108.
  • Fig. 3c shows a perspective view of a pumping chamber 108 arrangement wherein none of the channel 104 segments are tangentially attached to the pumping chamber 108. Instead, one of the segments is attached to the pumping chamber 108 axially, that is, along the axis of rotation of the magnetic rods.
  • the arrangements of Figs. 3a-3c are exemplary only. Numerous additional configurations are possible within the spirit and scope of the invention.
  • Figs. 4a - 4c show plan views of fluid flow through a microfluidic mixing and pumping device 100 in accordance with an embodiment of the present invention.
  • Fig. 4a shows the flow of two liquids A, B through the device 100 without the influence of the rotating magnetic field 102 or magnetic rods 116.
  • the two inlets 110 provide a first fluid A and a second fluid B into the channel 104.
  • the mixing zone 106 is identified as the place where mixing could take place in the presence of a rotating magnetic field 102 and magnetic rods 116. Without the influence of the rotating magnetic field 102 and the magnetic rods 116, the two fluids A, B exhibit laminar flow and do not readily mix.
  • the first fluid A and the second fluid B stay along opposite walls. What little mixing occurs is through diffusion, and the diffusion is not fast even on a micro-scale.
  • Fig. 4b shows an embodiment of the micro fluidic mixing and pumping device 100 including the rotating magnetic field 102 and the magnetic rods 116.
  • the magnetic rods 116 tend to self-assemble and rotate as a mass under the influence of the rotating magnetic field 102.
  • the large-aspect ratio of the magnetic rods 116 enhances the tendency of the rods 116 to arrange themselves in a parallel manner.
  • Fig. 4b shows that the magnetic rods 116 are arranged generally parallel to each other and aligned with the external magnetic field 102.
  • the orientation of the magnetic field 102 is at an angle to the main axis of the channel 104 and the rods 116 have arranged themselves in a manner to encompass the entire cross-sectional area of the channel 104.
  • Fig. 4c shows the same arrangement as Fig. 4b , but with the magnetic rods 116 rotated to an angle perpendicular with the main axis of the channel 104.
  • the arrangement of magnetic rods 116 in Fig. 4b was too large to fit within the channel 104 when oriented in a perpendicular manner. Therefore the rods 116 will automatically and continually rearrange themselves to fit within the available area. Any of the magnetic rods which may be displaced will remain with the plurality of magnetic rods 116, but will find a new placement. In this manner the plurality of rods 116, individually and collectively, act directly upon a large portion of the cross-sectional area of the channel 104.
  • the rotation of the magnetic rods 116 within the generally symmetric mixing zone 106 provides no net pumping effect.
  • the result is that the first and second fluids A, B are subject to forces which destroy their laminar flow, and vortices are visible in the mixed fluid C after the mixing zone 106. Thereby the first and second fluids A, B are mixed completely and rapidly.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Mixers With Rotating Receptacles And Mixers With Vibration Mechanisms (AREA)
EP08153497A 2008-03-28 2008-03-28 Appareil et procédé pour mélangeur et pompe microfluide Ceased EP2105202A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP08153497A EP2105202A1 (fr) 2008-03-28 2008-03-28 Appareil et procédé pour mélangeur et pompe microfluide
PCT/IB2009/051234 WO2009118689A1 (fr) 2008-03-28 2009-03-25 Appareil et procédé pour un mélangeur et une pompe microfluidiques

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Application Number Priority Date Filing Date Title
EP08153497A EP2105202A1 (fr) 2008-03-28 2008-03-28 Appareil et procédé pour mélangeur et pompe microfluide

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Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102513014A (zh) * 2011-12-13 2012-06-27 江苏大学 微流控系统层流磁力搅拌混沌混合方法与装置
CN102861526A (zh) * 2012-09-17 2013-01-09 江苏大学 一种微流控芯片的柔性磁动微混合方法与装置
CN104162379A (zh) * 2014-07-30 2014-11-26 江苏大学 一种微流控芯片磁珠混沌混合方法及装置
WO2015128725A1 (fr) 2014-02-28 2015-09-03 Dh Technologies Development Pte. Ltd. Éléments magnétiques de traitement de fluides
CN105863985A (zh) * 2016-04-21 2016-08-17 北京航空航天大学 磁响应复合界面驱动液体运动器件及其制备方法和应用
CN105940249A (zh) * 2014-01-29 2016-09-14 惠普发展公司，有限责任合伙企业 微流体阀
WO2017093896A1 (fr) * 2015-11-30 2017-06-08 Dh Technologies Development Pte. Ltd. Ensembles électromagnétiques pour le traitement de fluides
CN107029612A (zh) * 2016-11-08 2017-08-11 华中科技大学 一种基于共平面线圈组的微流控快速混合器
US9777305B2 (en) 2010-06-23 2017-10-03 Iti Scotland Limited Method for the assembly of a polynucleic acid sequence
WO2020016854A1 (fr) * 2018-07-20 2020-01-23 Dh Technologies Development Pte. Ltd. Structure d'ensemble bobine électromagnétique pour traiter des fluides et ses procédés de fabrication
CN111468018A (zh) * 2020-04-16 2020-07-31 西南交通大学 一种柔性主动式微混合器件集成系统及制备方法
EP3586006A4 (fr) * 2017-02-22 2020-12-23 Citrogene Inc. Micro-pompe rotative intégrée, son procédé d'intégration et de commande de mouvement
CN113351265A (zh) * 2021-05-26 2021-09-07 西安交通大学 一种基于微导线磁场驱动微流体磁混合的系统及加工方法

Families Citing this family (4)

* Cited by examiner, † Cited by third party
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US10286366B2 (en) 2012-09-24 2019-05-14 Hewlett-Packard Development Company, L.P. Microfluidic mixing device
US9409170B2 (en) 2013-06-24 2016-08-09 Hewlett-Packard Development Company, L.P. Microfluidic mixing device
US10913039B2 (en) 2016-07-06 2021-02-09 Hewlett-Packard Development Company, L.P. Microfluidic mixer
EP4384306A1 (fr) * 2021-08-12 2024-06-19 Academia Sinica Mélangeur microfluidique pour mélange tridimensionnel amélioré

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US20040114458A1 (en) 2002-10-08 2004-06-17 Commissariat A L'energie Atomique Device for mixing fluids

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Cited By (20)

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Publication number Priority date Publication date Assignee Title
US9777305B2 (en) 2010-06-23 2017-10-03 Iti Scotland Limited Method for the assembly of a polynucleic acid sequence
CN102513014B (zh) * 2011-12-13 2014-02-12 江苏大学 微流控系统层流磁力搅拌混沌混合方法与装置
CN102513014A (zh) * 2011-12-13 2012-06-27 江苏大学 微流控系统层流磁力搅拌混沌混合方法与装置
CN102861526A (zh) * 2012-09-17 2013-01-09 江苏大学 一种微流控芯片的柔性磁动微混合方法与装置
US11209102B2 (en) 2014-01-29 2021-12-28 Hewlett-Packard Development Company, L.P. Microfluidic valve
CN105940249A (zh) * 2014-01-29 2016-09-14 惠普发展公司，有限责任合伙企业 微流体阀
WO2015128725A1 (fr) 2014-02-28 2015-09-03 Dh Technologies Development Pte. Ltd. Éléments magnétiques de traitement de fluides
US20170074871A1 (en) * 2014-02-28 2017-03-16 DH Technologies Development Pte Ltd. Magnetic Elements for Processing Fluids
US10656147B2 (en) 2014-02-28 2020-05-19 Dh Technologies Development Pte. Ltd. Magnetic elements for processing fluids
CN104162379A (zh) * 2014-07-30 2014-11-26 江苏大学 一种微流控芯片磁珠混沌混合方法及装置
CN104162379B (zh) * 2014-07-30 2016-03-02 江苏大学 一种微流控芯片磁珠混沌混合方法及装置
WO2017093896A1 (fr) * 2015-11-30 2017-06-08 Dh Technologies Development Pte. Ltd. Ensembles électromagnétiques pour le traitement de fluides
CN108290166A (zh) * 2015-11-30 2018-07-17 Dh科技发展私人贸易有限公司 用于处理流体的电磁组合件
CN105863985A (zh) * 2016-04-21 2016-08-17 北京航空航天大学 磁响应复合界面驱动液体运动器件及其制备方法和应用
CN107029612A (zh) * 2016-11-08 2017-08-11 华中科技大学 一种基于共平面线圈组的微流控快速混合器
EP3586006A4 (fr) * 2017-02-22 2020-12-23 Citrogene Inc. Micro-pompe rotative intégrée, son procédé d'intégration et de commande de mouvement
WO2020016854A1 (fr) * 2018-07-20 2020-01-23 Dh Technologies Development Pte. Ltd. Structure d'ensemble bobine électromagnétique pour traiter des fluides et ses procédés de fabrication
CN111468018A (zh) * 2020-04-16 2020-07-31 西南交通大学 一种柔性主动式微混合器件集成系统及制备方法
CN113351265A (zh) * 2021-05-26 2021-09-07 西安交通大学 一种基于微导线磁场驱动微流体磁混合的系统及加工方法
CN113351265B (zh) * 2021-05-26 2022-10-25 西安交通大学 一种基于微导线磁场驱动微流体磁混合的系统的加工方法

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