WO2009150585A1 - Micro-fluidic systems based on actuator elements - Google Patents

Micro-fluidic systems based on actuator elements Download PDF

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Publication number
WO2009150585A1
WO2009150585A1 PCT/IB2009/052371 IB2009052371W WO2009150585A1 WO 2009150585 A1 WO2009150585 A1 WO 2009150585A1 IB 2009052371 W IB2009052371 W IB 2009052371W WO 2009150585 A1 WO2009150585 A1 WO 2009150585A1
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Prior art keywords
stimulus
micro
host material
actuation
actuator elements
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PCT/IB2009/052371
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French (fr)
Inventor
Johannes T. A. Wilderbeek
Grietje N. Mol
Dirk J. Broer
Jacob M. J. Den Toonder
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Koninklijke Philips Electronics N.V.
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Publication of WO2009150585A1 publication Critical patent/WO2009150585A1/en

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    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04DNON-POSITIVE-DISPLACEMENT PUMPS
    • F04D33/00Non-positive-displacement pumps with other than pure rotation, e.g. of oscillating type

Definitions

  • the present invention relates to micro-fluidic systems, to a method for the manufacturing of such micro-fluidic systems and to a method for controlling or manipulating a fluid flow through micro-channels of such micro-fluidic systems.
  • the micro-fluidic systems may, for example, be used in biotechnological and pharmaceutical applications and in micro- channel cooling systems in microelectronics applications.
  • Micro-fluidic systems according to embodiments of the present invention are compact, cheap and easy to process.
  • Micro-fluidics relates to a multidisciplinary field comprising physics, chemistry, engineering and biotechnology that studies the behavior of fluids at volumes thousands of times smaller than a common droplet.
  • Micro-fluidic components form the basis of so-called "lab-on-a-chip” devices or biochip networks, that can process microliter and nano liter volumes of fluid and conduct highly sensitive analytical measurements.
  • the fabrication techniques used to construct micro-fluidic devices are relatively inexpensive and are amenable both to highly elaborate, multiplexed devices and also to mass production.
  • micro-fluidic technologies enable the fabrication of highly integrated devices for performing several different functions on a same chip substrate.
  • Micro-fluidic chips are becoming a key foundation to many of today's fast- growing biotechnologies, such as rapid DNA separation and sizing, cell manipulation, cell sorting and molecule detection.
  • Micro-fluidic chip-based technologies offer many advantages over their traditional macrosized counterparts.
  • Micro-fluidics is a critical component in, amongst others, gene chip and protein chip development efforts.
  • there is a basic need for controlling the fluid flow that is, fluids must be transported, mixed, separated and directed through a micro-channel system consisting of channels with a typical width of about 0.1 mm.
  • a challenge in micro- fluidic actuation is to design a compact and reliable micro-fluidic system for regulating or manipulating the flow of complex fluids of variable composition, e.g. saliva and full blood, in micro-channels.
  • Various actuation mechanisms have been developed and are at present used, such as, for example, pressure-driven schemes, micro-fabricated mechanical valves and pumps, inkjet-type pumps, electro-kinetically controlled flows, and surface-acoustic waves.
  • MEMS micro-electro-mechanical systems
  • lab-on-a- chip devices such as cartridge-based biosensors attract substantial interest, both from academic and industrial point of view.
  • cartridge-based devices require a combination of multiple micro-fluidic functions on a small area. Examples of such micro-fluidic functions may be e.g. mixing and displacement of liquids, controlled chemical and physical reactions and separation and/or detection of components.
  • Fig. 1 illustrates actuation of a polymeric element using electrostatic interaction.
  • the element consists of a polymer covered with a thin metal layer.
  • the element In the off- state, the element is curled due to the internal mechanical stress resulting from processing of the element.
  • micro-fluidic system and a method according to embodiments of the invention enable realization and control of complex flow patterns within e.g. microchannels of diagnostic devices, which may be of great importance for effective displacement of fluids through microchannels.
  • the present invention provides a micro-fluidic system comprising at least one micro-channel.
  • the micro-fluidic system furthermore comprises: a plurality of ciliary actuator elements in the micro-channel, each ciliary actuator element comprising a host material and at least one component provided to the host material, and - stimulus application means adapted for applying a combination of at least a first and second stimulus to the plurality of ciliary actuator elements, the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
  • It is an advantage of a micro-fluidic system according to embodiments of the invention that it enables realization and control of complex flow patterns within e.g. microchannels of diagnostic devices, which may be of great importance for effective displacement of fluids through the microchannels.
  • the stimulus application means may be adapted for applying first and second stimuli to the plurality of ciliary actuator elements so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements.
  • the asymmetric motion can be an asymmetric geometrical, asymmetric temporal or asymmetric functional motion.
  • asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design.
  • asymmetric temporal motion is meant temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different.
  • Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
  • the stimulus application means may comprise at least one actuation means chosen from the list of magnetic actuation means, photonic or light induced actuation means, electrostatic actuation means or thermal actuation means.
  • the first and second stimulus may be different from each other.
  • the first and second stimulus may be a same stimulus.
  • the stimulus may e.g. be light and the first and second light beams may have different wavelength.
  • the stimulus may be application of a magnetic field and the first and second magnetic field may have a different rotation rate.
  • the stimulus application means may be adapted such that the second stimulus is applied after the first stimulus has been applied. According to other embodiments of the invention, the stimulus application means may be adapted such that the first stimulus and second stimulus are applied simultaneously.
  • the at least one component may be provided to the host material as a continuous layer.
  • the continuous layer may be a uniform layer or may be a patterned layer.
  • the at least one component may be provided to the host material as particles which are dispersed in the host material.
  • the at least one component may be provided to the host material so as to form hinge-like segments of the ciliary actuator element.
  • the host material may comprise at least one polymer.
  • the at least one component may comprise one or more photochromic moiety optionally comprising reactive groups, one or more mesogenic group optionally comprising reactive groups, a semiconductive material or monomers leading to a semiconductive polymer, an electrically conductive material in the form of electrically conductive films, particles and/or agglomerates, a magnetic material in the form of magnetic films, particles and/or agglomerates, the magnetic properties may e.g. be (super)paramagnetic or ferromagnetic, a combination of materials having polar and apolar nature optionally comprising reactive groups or a material comprising one or more ionic groups optionally comprising reactive groups and/or capable of forming hydrogen bonds.
  • the present invention provides a method for the manufacturing of a micro-fluidic system, the micro-fluidic system comprising at least one micro-channel.
  • the method comprises: - providing a plurality of ciliary actuator elements attached to an inner side of a wall of the micro-channel, each ciliary actuator element comprising a host material and at least one component provided to the host material, and providing stimulus application means adapted for applying a combination of at least a first and second stimulus to the plurality of ciliary actuator elements, the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
  • Providing stimulus application means may be performed by providing at least one actuation means chosen from the list of magnetic actuation means, photonic or light induced actuation means, electrostatic actuation means or thermal actuation means.
  • the present invention also provides a micro-fluidic system obtained by a method according to embodiments of the present invention.
  • the present invention provides a method for controlling or manipulating a fluid flow through a micro-channel of a micro-fluidic system, the micro- channel being provided with a plurality of ciliary actuator elements each comprising a host material and at least one component provided to the host material.
  • the method comprises: applying a first stimulus to the ciliary actuator elements for actuating one of the host material or one of the at least one component, and applying a second stimulus to the ciliary actuator elements for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
  • Applying a first stimulus and applying a second stimulus to the plurality of ciliary actuator element may be performed so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements.
  • the asymmetric motion can be an asymmetric geometrical, asymmetric temporal or asymmetric functional motion.
  • asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design.
  • asymmetric temporal motion is meant temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different.
  • Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
  • Applying a first stimulus may be performed by means of magnetic actuation, photonic or light induced actuation, electrostatic actuation or thermal actuation.
  • Applying a second stimulus may be performed by means of magnetic actuation, photonic or light induced actuation, electrostatic actuation or thermal actuation.
  • applying a second stimulus may be performed after the first stimulus has been applied. According to other embodiments of the invention, applying a first stimulus and applying a second stimulus may be performed simultaneously.
  • the present invention provides a controller for controlled driving a stimulus application means of a micro-fluidic system comprising a plurality of ciliary actuator elements each comprising a host material and at least one component provided to the host material.
  • the controller comprises a control unit for controlled driving of actuation means of the stimulus application means so as to apply a first stimulus and a second stimulus to the ciliary actuator elements of the micro-fluidic system, the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
  • the controller may be adapted for causing an asymmetric motion of each of the plurality of ciliary actuator elements.
  • the asymmetric motion can be an asymmetric geometrical, asymmetric temporal or asymmetric functional motion.
  • asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design.
  • asymmetric temporal motion is meant temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different.
  • Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
  • the invention also provides a computer program product for performing, when executed on a computing means, a method according to embodiments of the invention.
  • the present invention also provides a machine readable data storage device storing the computer program product according to embodiments of the invention.
  • the present invention also provides a transmission of the computer program product according to embodiments of the invention over a local or wide area telecommunications network.
  • Fig. 1 illustrates actuation of a polymeric element using electrostatic interaction according to the prior art.
  • Fig. 2 illustrates an example of a ciliary beat cycle showing the effective and recovery strokes.
  • Fig. 3 illustrates a wave of cilia showing their co-ordination in a metachronic wave.
  • Fig. 4 to Fig. 6 illustrate examples of actuator elements 10 according to embodiments of the present invention.
  • Fig. 7 schematically shows a micro-fluidic system according to embodiments of the present invention.
  • Fig. 8 illustrates the principle of asymmetric actuation of actuator elements according to embodiments of the invention.
  • Fig. 9 shows examples of components which can be incorporated in a host material to obtain photonic actuation according to embodiments of the invention.
  • Fig. 10 illustrates an example of absorption spectra for the two photo-isomers of an azobenzene component.
  • Fig. 11 illustrates chemical structures of components which may be used to form polymer actuator elements suitable to be actuated by a combination of magnetic actuation and photonic actuation according to embodiments of the invention.
  • Fig. 12 shows snapshots of an actuation process of an actuator elements according to embodiments of the invention.
  • Fig. 13 schematically illustrates a system controller for use with a micro- fluidic system according to embodiments of the present invention.
  • Fig. 14 is a schematic representation of a processing system as can be used for performing a method according to embodiments of the present invention.
  • the present invention provides a micro-fluidic system, a method for the manufacturing of such a micro-fluidic system and a method for controlling or manipulating a fluid flow through micro-channels of such a micro-fluidic system.
  • actuation of actuator elements is effected by an external stimulus, which may be one of heat, electrical stimulation, magnetism or interaction with light.
  • the present invention now proposes the use of a combination of stimuli which results in an asymmetric geometrical or functional motion of the actuator elements.
  • a functional asymmetry may be desirable for the effective (forward) and recovery stroke of the actuation of the actuator elements (see further).
  • controllable geometrical or functional asymmetry may be advantageous not only for the net displacement of the fluid, but also to provide control over the realization and control of complex flow patterns of the fluid in the first place. This is of high importance for the realization of lab-on-a-chip type of applications where micro -fluidics play a most prominent role.
  • micro-fluidic system and methods according to embodiments of the present invention may be used in biotechno logical applications, such as micro total analysis systems, micro-fluidic diagnostics, micro-factories and chemical or biochemical micro- plants, biosensors, rapid DNA separation and sizing, cell manipulation and sorting, in pharmaceutical applications, in particular high-throughput combinatorial testing where local mixing is essential, and in micro-channel cooling systems e.g. in micro-electronics applications.
  • the present invention provides a micro-fluidic system comprising at least one micro-channel having a wall with an inner side.
  • the micro- fluidic system furthermore comprises: a plurality of ciliary actuator elements attached to the inner side of the wall, each ciliary actuator element comprising a host material and at least one component provided to the host material, and stimulus application means adapted for applying a combination of at least a first and a second stimulus to the plurality of ciliary actuator elements, the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
  • the stimulus application means may be adapted for applying first and second stimuli so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements.
  • the actuator elements exhibit an oscillatory motion consisting of cycles, where each cycle consists of a "forward" and a "backward” stroke (see above).
  • the motion is said to be "asymmetric" when the path of motion of the forward and the backward stroke do not coincide.
  • the asymmetric motion can be an asymmetric geometrical, an asymmetric temporal, or an asymmetric functional motion.
  • asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design.
  • asymmetric temporal motion is meant by temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different.
  • Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
  • micro-fluidic system enables realization and control of complex flow patterns of fluids within e.g. microchannels of diagnostic devices, which may be of high importance for effective displacement of the fluids through the microchannels.
  • a micro-fluidic system comprises at least one micro-channel and integrated micro-fluidic elements, also called integrated actuator elements, at an inner side of a wall of the at least one micro-channel.
  • the actuator elements may be, for example, in any of the embodiments of the present invention unimorphs or bimorphs or multimorphs.
  • the way in which the micro-actuators, especially for example polymer micro-actuators according to embodiments of the invention are envisioned to work is inspired by nature. Nature knows various ways to manipulate fluids at small scales, i.e. 1-100 micron scales. One particular mechanism found is that due to a covering of beating cilia over the external surface of micro-organisms, such as, for example, Paramecium, pleurobrachia, and opaline. Ciliary motile clearance is also used in the bronchia and nose of mammals to remove contaminants.
  • a cilium can be seen as a small hair or flexible rod which in, for example, protozoa may have a typical length of 10 ⁇ m and a typical diameter of 0.1 ⁇ m, attached to a surface.
  • Other functions of cilia are in cleansing of gills, feeding, excretion and reproduction.
  • the human trachea for example, is covered with cilia that transport mucus upwards and out of the lungs.
  • Cilia are also used to produce feeding currents by sessile organisms that are attached to a rigid substrate by a long stalk.
  • the combined action of the cilia movement with the periodic lengthening and shortening of the stalk induces a chaotic vortex. This results in chaotic filtration behavior of the surrounding fluid.
  • cilia can be used for transporting and/or mixing fluid in micro-channels.
  • the mechanics of ciliary motion and flow has interested both zoologists and fluid mechanists for many years.
  • the beat of a single cilium can be separated into two distinct phases i.e. a fast effective stroke (curve 1 to 3 of Fig. 2) when the cilium drives fluid in a desired direction and a recovery stroke (curve 4 to 7 of Fig. 2) when the cilium seeks to minimize its influence on the generated fluid motion.
  • a fast effective stroke curve 1 to 3 of Fig. 2
  • a recovery stroke curve 4 to 7 of Fig. 2
  • fluid motion is caused by high concentrations of cilia in rows along and across the surface of an organism.
  • the movements of adjacent cilia in one direction are out of phase, this phenomenon is called metachronism.
  • Fig. 3 illustrates such a wave 8 of cilia showing their co-ordination in a metachronic wave.
  • a model that describes the movement of fluid by cilia is published by J. Blake in 'A model for the micro-structure in ciliated organisms', J. Fluid. Mech. 55, p.1-23 (1972).
  • J. Blake in 'A model for the micro-structure in ciliated organisms', J. Fluid. Mech. 55, p.1-23 (1972).
  • the influence of cilia on fluid flow is modeled by representing the cilia as a collection of "Stokeslets" along their centerline, which can be viewed as point forces within the fluid. The movement of these Stokeslets in time is prescribed, and the resulting fluid flow can be calculated.
  • the approach of a preferred aspect of the present invention makes use of this to mimic the cilia- like fluid manipulation in micro -channels by covering the walls of the micro-channels with "artificial cilia" based on microscopic polymer actuator elements, i.e. polymer structures changing their shape and/or dimension in response to a certain external stimulus.
  • microscopic actuator elements such as polymer actuator elements may also be referred to as actuators, e.g.
  • the actuator elements comprise a host material and at least one component provided to the host material.
  • the host material may, for example, be based on polymer materials. Suitable materials that may be used as a host material may be found in the book "Electroactive Polymer (EAP) Actuators as Artificial Muscles", ed. Bar-Cohen, SPIE Press, 2004. However, also other materials may be used as a host material for the actuator elements.
  • EAP Electroactive Polymer
  • the materials that may be used as a host material to form actuator elements according to embodiments of the present invention should be such that the formed actuator elements have the following characteristics: - the actuator elements should be compliant, i.e.
  • the actuator elements should be tough, not brittle, the actuator elements should respond to a certain stimulus such as e.g. light, an electric field, a magnetic field, etc. by bending or changing shape, and the actuator elements should be easy to process by means of relatively cheap processes.
  • the materials used to form the actuator elements may have to be functionalized.
  • polymers are preferred for at least a part of the actuators, e.g. for the host material.
  • Most types of polymers can be used according to embodiments of the present invention, except for very brittle polymers such as e.g. polystyrene which are not very suitable to use with the present invention.
  • metals may be used to form the actuator elements or may be part of the actuator elements, e.g. in Ionomeric Polymer-Metal composites (IPMC).
  • IPMC Ionomeric Polymer-Metal composites
  • all suitable materials i.e. materials that are able to change shape by, for example, mechanically deforming as a response to an external stimulus
  • may be electro-active piezoelectric ceramics such as, for example, barium titanate, quartz or lead zirconate titanate (PZT). These materials may respond to an applied external stimulus, such as for example an applied electric field, by expanding.
  • PZT lead zirconate titanate
  • electro-active ceramics an important drawback of electro-active ceramics is that they are brittle, i.e. they fracture quite easily.
  • the processing technologies for electro- active ceramics are rather expensive and cannot be scaled up to large surface areas.
  • electro-active piezoelectric ceramics may only be suitable in a limited number of cases.
  • SMA's shape memory alloys
  • SMA's are metals that demonstrate the ability to return to a memorized shape or size when they are heated above a certain temperature. The stimulus here is thus change in temperature. Generally, those metals can be deformed at low temperature and will return to their original shape upon exposure to a high temperature, by virtue of a phase transformation that happens at a critical temperature.
  • SMA's may be NiTi or copper-aluminium-based alloys (e.g. CuZnAl and CuAl).
  • SMA's have some drawbacks and thus limitations in the number of cases in which these materials may be used to form actuator elements. The alloys are relatively expensive to manufacture and machine, and large surface area processing is not easy to do.
  • EAPs Electroactive Polymers
  • The may be classified very generally into two classes: ionic and electronic.
  • Electronically activated EAPs include any of electrostrictive (e.g. electrostrictive graft elastomers), electrostatic (dielectric), piezoelectric, magnetic, electrovisco-elastic, liquid crystal elastomer, and ferroelectric actuated polymers.
  • Ionic EAPs include gels such as ionic polymer gels, Ionomeric Polymer-Metal Composites (IPMC), conductive polymers and carbon nanotubes.
  • the materials may exhibit conductive or photonic properties, or be chemically activated, i.e. be non-electrically deformable. Any of the above EAPs can be made to bend with a significant curving response and can be used in the form, for example, of ciliary actuators. Because of the above, according to embodiments of the present invention, the host material of the actuator elements may be formed of, or include as a part of their construction, polymer materials. Polymer materials are, generally, tough instead of brittle, relatively cheap, elastic up to large strains (up to 10%) and offer perspective of being processable on large surface areas with simple processes.
  • Actuator elements formed of materials which can respond to temperature changes, visible and UV light, water, molecules, electrostatic field, magnetic field, electric field, may be used according to embodiments of the invention. Suitable materials can be identified from the above book by Bar-Cohen.
  • the basic idea of the invention which is based on artificial cilia manipulating fluids on a small scale is independent of the material the actuator means is formed of.
  • light- and magnetic actuation means may be preferred, considering possible interactions with the complex biological fluids that may occur using other materials to form the actuator elements.
  • the actuator elements furthermore comprise at least one component which is provided to the host material.
  • the at least one component may comprise one or more photochromic moiety, which may optionally comprise reactive groups, one or more mesogenic group which may optionally comprise reactive groups, a semiconductive material or monomers leading to a semiconductive polymer, an electrically conductive material e.g. in the form of electrically conductive films, particles and/or agglomerates, a magnetic material e.g. in the form of magnetic films, particles and/or agglomerates, the magnetic properties may e.g.
  • the material used for forming the actuator elements 10, i.e. the host material provided with the at least one component may also be referred to as multiple-stimuli materials, e.g. two-stimuli materials.
  • Fig. 4 to Fig. 6 illustrate examples of actuator elements 10 according to embodiments of the present invention. It has to be understood that these examples are only for the purpose of illustration and are not intended to limit the invention in any way.
  • the actuator elements 10 may comprise a host material 11, e.g. polymer material and a component 12 provided in or on the host material 11, e.g. polymer material in the form of a continuous layer.
  • This layer may, for example, be a conductive or semiconductive layer or a magnetic layer.
  • the component 12 in the form of a continuous layer may be positioned at the top (upper drawing of Fig. 4) or at the bottom of the actuator element 10 (drawing in the middle of Fig. 4), or may be situated in the centre of the actuator element 10 (lower drawing of Fig. 4).
  • the continuous layer may, for example, be deposited as a uniform layer.
  • the continuous layer may also be patterned (not shown in the drawings) to increase the compliance and ease of deformation of the actuator elements 10.
  • the material the continuous layer is formed of depends on the actuation mechanism that will be used.
  • the component 12 may be provided as a magnetic layer.
  • the magnetic layer may, for example, be an electroplated permalloy, e.g. Ni-Fe and may, for example, have a thickness of between 0.1 ⁇ m and 10 ⁇ m.
  • the actuator elements 10 may comprise a host material 11, e.g. polymer material and a component 12 in the form of particles.
  • the host material 11, e.g. polymer material may in that case function as a matrix in which the particles are dispersed.
  • the particles may be added to the polymer in solution or may be added to monomers that, later on, then can be polymerized.
  • the polymer may then be applied to the inner side of wall of a micro-channel by any suitable method, e.g. by a wet deposition technique such as e.g. spin-coating.
  • the particles may, for example, be spherical, as is illustrated in the upper tow drawings in Fig. 5 or may be elongated, e.g. rod- shaped, as is illustrated in the lower drawing of Fig. 5.
  • Rod-shaped particles may have an advantage of automatically being aligned by shear flow during the deposition process.
  • the particles may be randomly arranged in the host material matrix, as is illustrated in the upper and lower drawing of Fig. 5 or they may be arranged or aligned in the host material matrix in a regular pattern, e.g. in rows, as is illustrated in the drawing in the middle of Fig. 5.
  • the component 12 may be provided in the host material 11, e.g. polymer material as magnetic particles.
  • the magnetic particles may, for example, be ferro- or ferri-magnetic particles, or (super)paramagnetic particles, comprising, for example, elements such as cobalt, nickel, iron, ferrites.
  • the magnetic particles may be superparamagnetic particles, i.e. they do not have a remanent magnetic field when an applied magnetic field has been switched off, especially when elastic recovery of the polymer is slow compared to magnetic field modulation. Long off-time of the magnetic field may save power consumption.
  • Fig. 6 illustrates another example of an actuator element 10 according to embodiments of the invention.
  • the actuator element 10 may comprise different segments. Segments formed by the host material 11, e.g. polymer material may alternate with segments formed by the at least one component 12. The segments of the at least one component 12 may act as hinges (see further) when the actuator element 10 is being actuated. These hinge-like segments are geometrically distributed within the host material 11.
  • the actuator elements 10 may be polymer MEMS (micro-electromechanical system) which may, for example, have a rod-like shape or a beam-like shape.
  • Fig. 7 schematically illustrates a micro-fluidic system 100 according to an embodiment of the invention.
  • a plurality of actuator elements 10 is arranged on an inner side 13 of a wall 14 of a micro-channel 15.
  • a cross-section of a micro-channel 15 is schematically depicted.
  • a plurality of straight actuator elements 10 is provided onto the inner side 13 of the wall 14 of the micro-channel 15.
  • the actuator elements 10 Upon actuation, i.e. under the action of external stimuli the actuator elements 10 can move back and forth and can change their shape (see further).
  • the actuator elements 10 may be arranged in one or more rows.
  • the actuator elements 10 may be arranged in two rows of actuator elements 10, i.e.
  • the actuator elements 10 may also be arranged in a plurality of rows of actuator elements 10 which may be arranged to form, for example, a two-dimensional array.
  • the actuator elements 10 may be randomly positioned at the inner side 13 of the wall 14 of the micro-channel 15.
  • the micro-fluidic system 100 furthermore comprises stimulus application means 16, which is schematically illustrated in Fig. 7 and which is adapted for applying a combination of at least a first and a second stimulus to the plurality of ciliary actuator elements 10.
  • the first stimulus is for actuating one of the host material or one of the at least one component provided to the host material
  • the second stimulus is for actuating one of the host material or one of the at least one component provided to the host material.
  • the first and second stimuli are for actuating different materials.
  • the stimulus application means may be adapted for applying first and second stimuli so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements 10.
  • the asymmetric motion may be a geometrical or functional asymmetric motion.
  • the stimulus application means 16 may be adapted for first applying the first stimulus and subsequently applying the second stimulus.
  • the first and second stimulus may be different stimuli or may be a same stimulus.
  • the stimulus may e.g. be light and the first and second light beams may have different wavelength.
  • the stimulus may be application of a magnetic field and the first and second magnetic field may have a different rotation rate.
  • the stimulus application means 16 may be adapted for simultaneously applying the first stimulus and the second stimulus.
  • the stimulus application means 16 may, for example, comprise a combination of at least two actuation means chosen from the list of magnetic actuation means, photonic or light induced actuation means, electrostatic actuation means or thermal actuation means.
  • the stimulus application means 16 may comprise at least two different actuation means for applying two different stimuli, or may comprise a same actuation means for at least twice applying a same stimulus.
  • Fig. 8 illustrates an example of asymmetric motion of a ciliary actuator element 10 obtained by using a stimulus application means 16 adapted according to embodiments of the present invention.
  • the ciliary actuator element 10 is provided on the inner side 13 of a wall 14 of a microchannel 15 (see Fig. 8a).
  • the stimulus application means 16 may comprise a magnetic actuation means 17 and a light induced actuation means 18.
  • the actuation of the actuator elements 10 is, according to the present example, initially effected magnetically, resulting in a bending of the actuator element 10 around a 'hinge' (indicated with reference number 19 in Fig. 8b) situated at a bottom of the actuator element 10 (see Fig.
  • asymmetric motion of the actuator elements 10 may be achieved by providing the at least one component 12 as hinge-like segments 19, 20 that are geometrically distributed within the host material 11, as schematically shown in Fig. 8, and as already illustrated and discussed with respect to Fig. 6.
  • the realization of asymmetric actuation does not depend on a geometrical hinge-like design as illustrated in Fig. 6 and Fig. 8.
  • the at least one component 12 may be in the form of particles (see Fig. 5) which may be distributed homogeneously within the host material 11.
  • the dispersed particles which may be magnetic particles and photochromic moieties, will respond to the applied external stimuli, in the example given magnetic and photonic actuation, throughout the entire material.
  • the dispersed particles which may be magnetic particles and photochromic moieties, will respond to the applied external stimuli, in the example given magnetic and photonic actuation, throughout the entire material.
  • geometrical intermediate designs can be envisioned and are also part of the present invention.
  • the intra-molecular geometry of the actuator element 10 is thus independently changed by a combination of first and second, e.g. magnetic and photonic, actuation as separate stimuli.
  • the magnetic actuation can be realized through the incorporation of dispersed magnetic particles, or the incorporation of concentrated regions of magnetic elements, for example through the use of magnetic films deposited on the matrix or incorporated within the matrix. Of course, combinations thereof can also be envisioned.
  • the magnetic particles or films may exhibit ferromagnetism, or (super)paramagnetism, depending on the desired actuation characteristics.
  • the magnetic particles will usually be stabilized via a tailored stabilizer, for example (block-co)polymers or ionic groups.
  • Photonic actuation can be obtained by using a photoresponsive material as a component 12 provided to, e.g. in or on, the host material.
  • the photoresponsive material may comprise chromophores which lead to photochromism.
  • Photochromism is defined as a reversible phototransformation of a chemical species between two forms with different absorption spectra.
  • other properties may change, such as e.g. the refractive index, dielectric constant and geometrical structure.
  • Particular non- limitative examples of materials that may be used with photonic actuation according to embodiments of the invention may be azobenzenes (see Fig. 9(a)), spirobenzopyranes (see Fig.
  • Fig. 10 shows typical absorption spectra for the two photo-isomers of an azobenzene compound (see Fig. 9(a)), in its respective E (trans) and Z (cis) state.
  • the energetically most stable conformation, the E-state can be converted to its corresponding Z-state using UV light.
  • the resulting Z-state can be converted back using longer wavelength light (e.g. visible light), but also using for example a thermal driving force.
  • the latter is usually already governed by ambient temperatures. Consequently, the Z- state of these materials is usually not stable over time, even in the dark, and can relax back in hours to seconds, even milliseconds.
  • the chromophores may be incorporated in the host material 11 via reactive groups, e.g. acrylate groups, epoxides, in a polymer matrix, such as a polymer network.
  • reactive groups e.g. acrylate groups, epoxides
  • the absorption can be controlled even further using polarized light for the photonic actuation. The effectiveness will strongly depend on the morphology of the host system.
  • Fig. 11 illustrates an example of a system of components 12 that can be incorporated in the host material 11 to form an actuator element according to an embodiments of the invention and suitable to be used with a combination of magnetic and photonic actuation.
  • a system comprising one or more acrylate monomers containing azobenzene moieties, one or more non-photochromic groups containing acrylates, stabilized superparamagnetic particles (e.g. Fe 3 O 4 nanoparticles with a diameter of about 10 nm and dispersed in a carrier fluid, e.g. N-methylpyrrolidon, on 50% w/w basis), a photoinitiator (e.g.
  • Irgacure 651 or Irgacure 819) or thermal initiator e.g. AIBN (2,2'-Azobisisobutyronitrile)
  • thermal initiator e.g. AIBN (2,2'-Azobisisobutyronitrile)
  • no use was made of the mesogenic order, by enforcing a multi- domain structure of the liquid crystalline network.
  • Selective control of the actuation direction was achieved by introducing an absorption gradient over the film, caused by the presence of the magnetic particles. Snapshots of the actuation process of a film produced by this example are shown in Fig. 12.
  • the polymeric film comprising superparamagnetic particles and azobenzene moieties and forming an actuator element 10 according to an embodiment of the present invention had a thickness of 5 ⁇ m.
  • the actuator element 10 is fixed in a clamp 21 and positioned near a magnetic pole, which acts as a magnetic actuation means 17.
  • a light source was provided (not shown in the Figure).
  • Fig. 12(a) shows the initial situation. Both the magnetic field and the light source are switched off. For clarity issues, the shape of the actuator element 10 is indicated by dashed lines.
  • the actuator element 10 is attracted to the magnetic pole 15 (see Fig. 12(b)).
  • the actuator element 10 moved away from the magnetic pole 15 (see Fig. 12(c)).
  • the light source was switched on to illuminate part of the actuator element 10. As can be seen from Fig. 12(d) to Fig. 12(f) the illuminated part 22 of the actuator element 10 deformed.
  • liquid crystalline carrier was replaced by an intrinsically isotropic polymeric matrix, consisting of a low Young's modulus polyetherurethaneacrylate with variable molecular weight. Again, an absorption gradient was introduced by the presence of magnetic particles.
  • a (stacked) magnetic film may be used.
  • a film is envisioned by polymerizing a mixture consisting of an apolar monomer (e.g. hexanediol diacrylate), a polar monomer (e.g. 3- hydroxypropyl acrylate), a photoinitiator (e.g. Irgacure 651), and optionally a light absorbing component with a preferential absorption in the wavelength region similar to the excitation wavelength region of the employed photoinitiator (e.g. Tinuvin 928), in the presence of (ferro- or para-)magnetic particles.
  • an apolar monomer e.g. hexanediol diacrylate
  • a polar monomer e.g. 3- hydroxypropyl acrylate
  • a photoinitiator e.g. Irgacure 651
  • a light absorbing component with a preferential absorption in the wavelength region similar to the excitation wavelength region of the employed photoinitiator e.g.
  • the present invention is not limited to the stimulation or actuation of actuator elements as described above, i.e. to a combination of magnetic actuation and photonic actuation.
  • Other combinations of first and second stimuli such as for example but not limited to, magnetic and electrostatic actuation, electrostatic and photonic actuation, magnetic and thermal actuation, etc. can also be envisioned.
  • a same actuation may be performed at least twice.
  • a host material for instance comprising at least one polymer component:
  • a polymer host may be formed in-situ from a monomer or mixture of different monomers.
  • An optional initiator allowing for the in-situ formation of the host, using either thermal initiation including room temperature conditions, photonic actuation of variable wavelengths, or combinations thereof.
  • Optional additives such as sensitizers, radical scavengers and inhibitors, UV-stabilizers, absorbing species such as colorants and pigments, agents capable of inducing helical twisting power, transfer agents, stabilizers, buffering components, complexation agents of any kind.
  • a semi-conductive material such as semi-conductive polymers, or monomers potentially leading to the formation of semi-conductive polymers.
  • An electrically conductive component that may be present in the form of incorporated electrically conductive films, particles and/or agglomerates.
  • a magnetic component that may be present in the form of incorporated magnetic films, particles and/or agglomerates.
  • the magnetic properties can, for example, be (super)paramagnetic or ferromagnetic.
  • a micro-fluidic system according to embodiments of the invention may have at least one of the following advantages:
  • actuator elements 10 e.g. polymeric micro-actuators.
  • a method for controlling or manipulating a fluid flow through a micro-channel 15 of a micro-fluidic system 100, the micro-channel 15 having a wall 13 with an inner side 14 being provided with a plurality of ciliary actuator elements 10, each ciliary actuator element 10 comprising a host material 11 and at least one component 12 provided to the host material 11, the method comprising: applying a first stimulus to the ciliary actuator elements 10 for actuating one of the host material 11 or one of the at least one component 12, and - applying a second stimulus to the ciliary actuator elements 10 for actuating one of the host material 11 or one of the at least one component 12, the first and second stimuli being for actuating different materials.
  • Applying a first stimulus and applying a second stimulus may be performed so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements 10.
  • the asymmetric motion can be an asymmetric geometrical, asymmetric temporal or asymmetric functional motion.
  • asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design.
  • asymmetric temporal motion is meant temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different.
  • Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
  • Applying a first stimulus and applying a second stimulus may be performed by means of magnetic actuation, photonic or light induced actuation, electrostatic actuation or thermal actuation.
  • applying a second stimulus may be performed after the first stimulus has been applied.
  • the first stimulus and second stimulus may be different or may be the same. In the latter case, for example, according to embodiments of the invention, the stimulus may e.g. be light and the first and second light beams may have different wavelength.
  • the stimulus may be application of a magnetic field and the first and second magnetic field may have a different rotation rate.
  • applying the first stimulus and applying the second stimulus may be performed simultaneously.
  • the present invention also provides a system controller 25 for use in a micro-fluidic system 100 according to embodiments of the present invention for controlled driving a stimulus application means 16 of the micro-fluidic system 100.
  • the system controller 25, which is schematically illustrated in Fig. 13, may comprise a control unit 26 for controlled driving of actuation means of the stimulus application means 16 for applying a first stimulus and a second stimulus to ciliary actuator elements 10 of the micro- fluidic system 100 so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements 10.
  • the system controller 25 may include a computing device, e.g. microprocessor, for instance it may be a micro-controller.
  • a programmable controller for instance a programmable digital logic device such as a Programmable Array Logic (PAL), a Programmable Logic Array, a Programmable Gate Array, especially a Field Programmable Gate Array (FPGA).
  • PAL Programmable Array Logic
  • FPGA Field Programmable Gate Array
  • Fig. 14 shows one configuration of processing system 200 that includes at least one customizable or programmable processor 41 coupled to a memory subsystem 42 that includes at least one form of memory, e.g., RAM, ROM, and so forth.
  • the processor 41 or processors may be a general purpose, or a special purpose processor, and may be for inclusion in a device, e.g., a chip that has other components that perform other functions.
  • one or more aspects of the method according to embodiments of the present invention can be implemented in digital electronic circuitry, or in computer hardware, firmware, software, or in combinations of them.
  • the processing system may include a storage subsystem 43 that has at least one disk drive and/or CD-ROM drive and/or DVD drive.
  • a display system, a keyboard, and a pointing device may be included as part of a user interface subsystem 44 to provide for a user to manually input information, such as parameter values. More elements such as network connections, interfaces to various devices, and so forth, may be included, but are not illustrated in Fig. 14.
  • the various elements of the processing system 40 may be coupled in various ways, including via a bus subsystem 45 shown in Fig. 14 for simplicity as a single bus, but will be understood to those in the art to include a system of at least one bus.
  • the memory of the memory subsystem 42 may at some time hold part or all (in either case shown as 46) of a set of instructions that when executed on the processing system 40 implement the steps of the method embodiments described herein.
  • the present invention also includes a computer program product which provides the functionality of any of the methods according to embodiments of the present invention when executed on a computing device.
  • Such computer program product can be tangibly embodied in a carrier medium carrying machine-readable code for execution by a programmable processor.
  • the present invention thus relates to a carrier medium carrying a computer program product that, when executed on computing means, provides instructions for executing any of the methods as described above.
  • carrier medium refers to any medium that participates in providing instructions to a processor for execution. Such a medium may take many forms, including but not limited to, non-volatile media, and transmission media.
  • Non-volatile media includes, for example, optical or magnetic disks, such as a storage device which is part of mass storage.
  • Computer readable media include, a CD-ROM, a DVD, a flexible disk or floppy disk, a tape, a memory chip or cartridge or any other medium from which a computer can read.
  • Various forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution.
  • the computer program product can also be transmitted via a carrier wave in a network, such as a LAN, a WAN or the Internet.
  • Transmission media can take the form of acoustic or light waves, such as those generated during radio wave and infrared data communications.
  • Transmission media include coaxial cables, copper wire and fiber optics, including the wires that comprise a bus within a computer.

Abstract

The present invention provides a micro-fluidic system (100) comprising at least one micro-channel (15). The micro-fluidic system (100) furthermore comprises in the micro-channel (15) a plurality of ciliary actuator elements (10) comprising a host material (11) and at least one component (12) provided to the host material (11), and stimulus application means (16) adapted for applying a combination of at least a first and second stimulus to the plurality of ciliary actuator elements (10). The first stimulus is for actuating one of the host material (11) or one of the at least one component (12), and the second stimulus is for actuating one of the host material or one of the at least one component (12), the first and the second stimuli being for actuating different materials. The present invention also provides a method for manufacturing such a micro-fluidic system (100) and a method for controlling or manipulating a fluid flow through a micro-channel (15) of such a micro-fluidic system (100). The micro-fluidic systems may, for example, be used in biotechno logical and pharmaceutical applications and in micro-channel cooling systems in microelectronics applications. Micro-fluidic systems according to embodiments of the present invention are compact, cheap and easy to process.

Description

Micro-fluidic systems based on actuator elements
TECHNICAL FIELD OF THE INVENTION
The present invention relates to micro-fluidic systems, to a method for the manufacturing of such micro-fluidic systems and to a method for controlling or manipulating a fluid flow through micro-channels of such micro-fluidic systems. The micro-fluidic systems may, for example, be used in biotechnological and pharmaceutical applications and in micro- channel cooling systems in microelectronics applications. Micro-fluidic systems according to embodiments of the present invention are compact, cheap and easy to process.
BACKGROUND OF THE INVENTION Micro-fluidics relates to a multidisciplinary field comprising physics, chemistry, engineering and biotechnology that studies the behavior of fluids at volumes thousands of times smaller than a common droplet. Micro-fluidic components form the basis of so-called "lab-on-a-chip" devices or biochip networks, that can process microliter and nano liter volumes of fluid and conduct highly sensitive analytical measurements. The fabrication techniques used to construct micro-fluidic devices are relatively inexpensive and are amenable both to highly elaborate, multiplexed devices and also to mass production. In a manner similar to that for microelectronics, micro-fluidic technologies enable the fabrication of highly integrated devices for performing several different functions on a same chip substrate. Micro-fluidic chips are becoming a key foundation to many of today's fast- growing biotechnologies, such as rapid DNA separation and sizing, cell manipulation, cell sorting and molecule detection. Micro-fluidic chip-based technologies offer many advantages over their traditional macrosized counterparts. Micro-fluidics is a critical component in, amongst others, gene chip and protein chip development efforts. In all micro-fluidic devices, there is a basic need for controlling the fluid flow, that is, fluids must be transported, mixed, separated and directed through a micro-channel system consisting of channels with a typical width of about 0.1 mm. A challenge in micro- fluidic actuation is to design a compact and reliable micro-fluidic system for regulating or manipulating the flow of complex fluids of variable composition, e.g. saliva and full blood, in micro-channels. Various actuation mechanisms have been developed and are at present used, such as, for example, pressure-driven schemes, micro-fabricated mechanical valves and pumps, inkjet-type pumps, electro-kinetically controlled flows, and surface-acoustic waves. The application of micro-electro-mechanical systems (MEMS) technology to micro-fluidic devices has spurred the development of micro-pumps to transport a variety of liquids at a large range of flow rates and pressures.
Anticipated increasing load on healthcare systems stimulates a shift of the diagnosis from a more laborious, time consuming and expensive, usually hospital-based centralized lab to the point of need. This will bring about a need to downscale analysis platforms with respect to physical size, cost and time to diagnosis. In this context, lab-on-a- chip devices such as cartridge-based biosensors attract substantial interest, both from academic and industrial point of view. These cartridge-based devices require a combination of multiple micro-fluidic functions on a small area. Examples of such micro-fluidic functions may be e.g. mixing and displacement of liquids, controlled chemical and physical reactions and separation and/or detection of components.
Although significant progress has already led to a variety of individual micro- fluidic components and principles, it is still difficult to integrate the individual components in a device, and the controlled displacement and routing of liquids, and/or homogenization/mixing requires the control over flow patterns ranging from relatively simple laminar flow patterns to very complex flow patterns.
In order to enable the realization and control of these flow patterns, versatile responsive materials have been realized in micro-fluidic devices. Previous studies have introduced a range of working principles and demonstrators based on novel responsive polymeric, micron-sized materials that can manipulate fluids by reversible micro-actuation. The actuation can be effected by various external stimuli, such as e.g. the use of heat, electrical stimulation, magnetism, and the interaction with light, and examples of these stimuli-assisted actuations have been described before.
Fig. 1 illustrates actuation of a polymeric element using electrostatic interaction. The element consists of a polymer covered with a thin metal layer. In the off- state, the element is curled due to the internal mechanical stress resulting from processing of the element. Upon application of a voltage, in the on- state, the element extends due to the electrostatic attraction.
It has been shown that arrays of such elements present on internal walls of micro-fluidic channels are highly efficient when using electrostatic stimulation, to induce flow transport and/or to induce mixing. Nevertheless, to fully realize and control desired flow patterns, an increased degree of control may be desired.
SUMMARY OF THE INVENTION It is an object of embodiments of the present invention to provide a micro- fluidic system, a method for the manufacturing of such a micro-fluidic system and a method for controlling or manipulating a fluid flow through micro-channels of such a micro-fluidic system.
It is an advantage of a micro-fluidic system and a method according to embodiments of the invention that they enable realization and control of complex flow patterns within e.g. microchannels of diagnostic devices, which may be of great importance for effective displacement of fluids through microchannels.
The above objective is accomplished by a method and device according to the present invention. In a first aspect, the present invention provides a micro-fluidic system comprising at least one micro-channel. The micro-fluidic system furthermore comprises: a plurality of ciliary actuator elements in the micro-channel, each ciliary actuator element comprising a host material and at least one component provided to the host material, and - stimulus application means adapted for applying a combination of at least a first and second stimulus to the plurality of ciliary actuator elements, the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials. It is an advantage of a micro-fluidic system according to embodiments of the invention that it enables realization and control of complex flow patterns within e.g. microchannels of diagnostic devices, which may be of great importance for effective displacement of fluids through the microchannels.
The stimulus application means may be adapted for applying first and second stimuli to the plurality of ciliary actuator elements so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements.
The asymmetric motion can be an asymmetric geometrical, asymmetric temporal or asymmetric functional motion. With asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design. By asymmetric temporal motion is meant temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different. Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
According to embodiments of the invention, the stimulus application means may comprise at least one actuation means chosen from the list of magnetic actuation means, photonic or light induced actuation means, electrostatic actuation means or thermal actuation means. According to embodiments of the invention, the first and second stimulus may be different from each other. According to other embodiments of the invention, the first and second stimulus may be a same stimulus. In this latter case, for example, according to embodiments of the invention, the stimulus may e.g. be light and the first and second light beams may have different wavelength. According to other embodiments, the stimulus may be application of a magnetic field and the first and second magnetic field may have a different rotation rate.
According to embodiments of the invention, the stimulus application means may be adapted such that the second stimulus is applied after the first stimulus has been applied. According to other embodiments of the invention, the stimulus application means may be adapted such that the first stimulus and second stimulus are applied simultaneously.
According to embodiments of the invention, the at least one component may be provided to the host material as a continuous layer. The continuous layer may be a uniform layer or may be a patterned layer.
According to other embodiments of the invention, the at least one component may be provided to the host material as particles which are dispersed in the host material.
According to still further embodiments of the invention, the at least one component may be provided to the host material so as to form hinge-like segments of the ciliary actuator element.
The host material may comprise at least one polymer.
The at least one component may comprise one or more photochromic moiety optionally comprising reactive groups, one or more mesogenic group optionally comprising reactive groups, a semiconductive material or monomers leading to a semiconductive polymer, an electrically conductive material in the form of electrically conductive films, particles and/or agglomerates, a magnetic material in the form of magnetic films, particles and/or agglomerates, the magnetic properties may e.g. be (super)paramagnetic or ferromagnetic, a combination of materials having polar and apolar nature optionally comprising reactive groups or a material comprising one or more ionic groups optionally comprising reactive groups and/or capable of forming hydrogen bonds.
In a second aspect, the present invention provides a method for the manufacturing of a micro-fluidic system, the micro-fluidic system comprising at least one micro-channel. The method comprises: - providing a plurality of ciliary actuator elements attached to an inner side of a wall of the micro-channel, each ciliary actuator element comprising a host material and at least one component provided to the host material, and providing stimulus application means adapted for applying a combination of at least a first and second stimulus to the plurality of ciliary actuator elements, the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
Providing stimulus application means may be performed by providing at least one actuation means chosen from the list of magnetic actuation means, photonic or light induced actuation means, electrostatic actuation means or thermal actuation means.
The present invention also provides a micro-fluidic system obtained by a method according to embodiments of the present invention.
In a third aspect, the present invention provides a method for controlling or manipulating a fluid flow through a micro-channel of a micro-fluidic system, the micro- channel being provided with a plurality of ciliary actuator elements each comprising a host material and at least one component provided to the host material. The method comprises: applying a first stimulus to the ciliary actuator elements for actuating one of the host material or one of the at least one component, and applying a second stimulus to the ciliary actuator elements for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
It is an advantage of a method according to embodiments of the invention that it enables realization and control of complex flow patterns within e.g. microchannels of diagnostic devices, which may be of great importance for effective displacement of fluids through the microchannels.
Applying a first stimulus and applying a second stimulus to the plurality of ciliary actuator element may be performed so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements.
The asymmetric motion can be an asymmetric geometrical, asymmetric temporal or asymmetric functional motion. With asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design. By asymmetric temporal motion is meant temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different. Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
Applying a first stimulus may be performed by means of magnetic actuation, photonic or light induced actuation, electrostatic actuation or thermal actuation.
Applying a second stimulus may be performed by means of magnetic actuation, photonic or light induced actuation, electrostatic actuation or thermal actuation.
According to embodiments of the invention, applying a second stimulus may be performed after the first stimulus has been applied. According to other embodiments of the invention, applying a first stimulus and applying a second stimulus may be performed simultaneously.
In a further aspect, the present invention provides a controller for controlled driving a stimulus application means of a micro-fluidic system comprising a plurality of ciliary actuator elements each comprising a host material and at least one component provided to the host material. The controller comprises a control unit for controlled driving of actuation means of the stimulus application means so as to apply a first stimulus and a second stimulus to the ciliary actuator elements of the micro-fluidic system, the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
The controller may be adapted for causing an asymmetric motion of each of the plurality of ciliary actuator elements.
The asymmetric motion can be an asymmetric geometrical, asymmetric temporal or asymmetric functional motion. With asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design. By asymmetric temporal motion is meant temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different. Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
In still a further aspect of, the invention also provides a computer program product for performing, when executed on a computing means, a method according to embodiments of the invention. The present invention also provides a machine readable data storage device storing the computer program product according to embodiments of the invention.
The present invention also provides a transmission of the computer program product according to embodiments of the invention over a local or wide area telecommunications network. The above and other characteristics, features and advantages of the present invention will become apparent from the following detailed description, taken in conjunction with the accompanying drawings, which illustrate, by way of example, the principles of the invention. This description is given for the sake of example only, without limiting the scope of the invention. The reference Figures quoted below refer to the attached drawings. Particular and preferred aspects of the invention are set out in the accompanying independent and dependent claims. Features from the dependent claims may be combined with features of the independent claims and with features of other dependent claims as appropriate and not merely as explicitly set out in the claims.
BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 illustrates actuation of a polymeric element using electrostatic interaction according to the prior art.
Fig. 2 illustrates an example of a ciliary beat cycle showing the effective and recovery strokes. Fig. 3 illustrates a wave of cilia showing their co-ordination in a metachronic wave.
Fig. 4 to Fig. 6 illustrate examples of actuator elements 10 according to embodiments of the present invention. Fig. 7 schematically shows a micro-fluidic system according to embodiments of the present invention.
Fig. 8 illustrates the principle of asymmetric actuation of actuator elements according to embodiments of the invention. Fig. 9 shows examples of components which can be incorporated in a host material to obtain photonic actuation according to embodiments of the invention.
Fig. 10 illustrates an example of absorption spectra for the two photo-isomers of an azobenzene component.
Fig. 11 illustrates chemical structures of components which may be used to form polymer actuator elements suitable to be actuated by a combination of magnetic actuation and photonic actuation according to embodiments of the invention.
Fig. 12 shows snapshots of an actuation process of an actuator elements according to embodiments of the invention.
Fig. 13 schematically illustrates a system controller for use with a micro- fluidic system according to embodiments of the present invention.
Fig. 14 is a schematic representation of a processing system as can be used for performing a method according to embodiments of the present invention.
In the different Figures, the same reference signs refer to the same or analogous elements.
DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS
The present invention will be described with respect to particular embodiments and with reference to certain drawings but the invention is not limited thereto but only by the claims. Any reference signs in the claims shall not be construed as limiting the scope. The drawings described are only schematic and are non-limiting. In the drawings, the size of some of the elements may be exaggerated and not drawn on scale for illustrative purposes.
Where the term "comprising" is used in the present description and claims, it does not exclude other elements or steps. Where an indefinite or definite article is used when referring to a singular noun e.g. "a" or "an", "the", this includes a plural of that noun unless something else is specifically stated.
Furthermore, the terms first, second and the like in the description and in the claims, are used for distinguishing between similar elements and not necessarily for describing a sequence, either temporally, spatially, in ranking or in any other manner. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other sequences than described or illustrated herein.
Moreover, the terms top, bottom and the like in the description and the claims are used for descriptive purposes and not necessarily for describing relative positions. It is to be understood that the terms so used are interchangeable under appropriate circumstances and that the embodiments of the invention described herein are capable of operation in other orientations than described or illustrated herein.
Reference throughout this specification to "one embodiment" or "an embodiment" means that a particular feature, structure or characteristic described in connection with the embodiment is included in at least one embodiment of the present invention. Thus, appearances of the phrases "in one embodiment" or "in an embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment, but may. Furthermore, the particular features, structures or characteristics may be combined in any suitable manner, as would be apparent to one of ordinary skill in the art from this disclosure, in one or more embodiments.
Similarly it should be appreciated that in the description of exemplary embodiments of the invention, various features of the invention are sometimes grouped together in a single embodiment, Figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of one or more of the various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the claimed invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects lie in less than all features of a single foregoing disclosed embodiment. Thus, the claims following the detailed description are hereby expressly incorporated into this detailed description, with each claim standing on its own as a separate embodiment of this invention.
Furthermore, while some embodiments described herein include some but not other features included in other embodiments, combinations of features of different embodiments are meant to be within the scope of the invention, and form different embodiments, as would be understood by those in the art. For example, in the following claims, any of the claimed embodiments can be used in any combination.
Furthermore, some of the embodiments are described herein as a method or combination of elements of a method that can be implemented by a processor of a computer system or by other means of carrying out the function. Thus, a processor with the necessary instructions for carrying out such a method or element of a method forms a means for carrying out the method or element of a method. Furthermore, an element described herein of an apparatus embodiment is an example of a means for carrying out the function performed by the element for the purpose of carrying out the invention. In the description provided herein, numerous specific details are set forth.
However, it is understood that embodiments of the invention may be practiced without these specific details. In other instances, well-known methods, structures and techniques have not been shown in detail in order not to obscure an understanding of this description.
The present invention provides a micro-fluidic system, a method for the manufacturing of such a micro-fluidic system and a method for controlling or manipulating a fluid flow through micro-channels of such a micro-fluidic system.
In known micro-fluidic systems actuation of actuator elements is effected by an external stimulus, which may be one of heat, electrical stimulation, magnetism or interaction with light. The present invention now proposes the use of a combination of stimuli which results in an asymmetric geometrical or functional motion of the actuator elements. For example, for effective displacement of liquids in micro-fluidic channels, a functional asymmetry may be desirable for the effective (forward) and recovery stroke of the actuation of the actuator elements (see further). As such, controllable geometrical or functional asymmetry may be advantageous not only for the net displacement of the fluid, but also to provide control over the realization and control of complex flow patterns of the fluid in the first place. This is of high importance for the realization of lab-on-a-chip type of applications where micro -fluidics play a most prominent role.
The micro-fluidic system and methods according to embodiments of the present invention may be used in biotechno logical applications, such as micro total analysis systems, micro-fluidic diagnostics, micro-factories and chemical or biochemical micro- plants, biosensors, rapid DNA separation and sizing, cell manipulation and sorting, in pharmaceutical applications, in particular high-throughput combinatorial testing where local mixing is essential, and in micro-channel cooling systems e.g. in micro-electronics applications. In a first aspect of the invention, the present invention provides a micro-fluidic system comprising at least one micro-channel having a wall with an inner side. The micro- fluidic system furthermore comprises: a plurality of ciliary actuator elements attached to the inner side of the wall, each ciliary actuator element comprising a host material and at least one component provided to the host material, and stimulus application means adapted for applying a combination of at least a first and a second stimulus to the plurality of ciliary actuator elements, the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
The stimulus application means may be adapted for applying first and second stimuli so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements. The actuator elements exhibit an oscillatory motion consisting of cycles, where each cycle consists of a "forward" and a "backward" stroke (see above). The motion is said to be "asymmetric" when the path of motion of the forward and the backward stroke do not coincide. The asymmetric motion can be an asymmetric geometrical, an asymmetric temporal, or an asymmetric functional motion. With asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design. By asymmetric temporal motion is meant by temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different. Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
It is an advantage of a micro-fluidic system according to embodiments of the invention that it enables realization and control of complex flow patterns of fluids within e.g. microchannels of diagnostic devices, which may be of high importance for effective displacement of the fluids through the microchannels.
A micro-fluidic system according to the invention comprises at least one micro-channel and integrated micro-fluidic elements, also called integrated actuator elements, at an inner side of a wall of the at least one micro-channel. The actuator elements may be, for example, in any of the embodiments of the present invention unimorphs or bimorphs or multimorphs.
In one aspect of the invention, the way in which the micro-actuators, especially for example polymer micro-actuators according to embodiments of the invention are envisioned to work, is inspired by nature. Nature knows various ways to manipulate fluids at small scales, i.e. 1-100 micron scales. One particular mechanism found is that due to a covering of beating cilia over the external surface of micro-organisms, such as, for example, Paramecium, pleurobrachia, and opaline. Ciliary motile clearance is also used in the bronchia and nose of mammals to remove contaminants. A cilium can be seen as a small hair or flexible rod which in, for example, protozoa may have a typical length of 10 μm and a typical diameter of 0.1 μm, attached to a surface. Apart from a propulsion mechanism for micro-organisms, other functions of cilia are in cleansing of gills, feeding, excretion and reproduction. The human trachea, for example, is covered with cilia that transport mucus upwards and out of the lungs. Cilia are also used to produce feeding currents by sessile organisms that are attached to a rigid substrate by a long stalk. The combined action of the cilia movement with the periodic lengthening and shortening of the stalk induces a chaotic vortex. This results in chaotic filtration behavior of the surrounding fluid.
The above discussion illustrates that cilia can be used for transporting and/or mixing fluid in micro-channels. The mechanics of ciliary motion and flow has interested both zoologists and fluid mechanists for many years. The beat of a single cilium can be separated into two distinct phases i.e. a fast effective stroke (curve 1 to 3 of Fig. 2) when the cilium drives fluid in a desired direction and a recovery stroke (curve 4 to 7 of Fig. 2) when the cilium seeks to minimize its influence on the generated fluid motion. In nature, fluid motion is caused by high concentrations of cilia in rows along and across the surface of an organism. The movements of adjacent cilia in one direction are out of phase, this phenomenon is called metachronism. Thus, the motion of cilia appears as a wave passing over the organism. Fig. 3 illustrates such a wave 8 of cilia showing their co-ordination in a metachronic wave. A model that describes the movement of fluid by cilia is published by J. Blake in 'A model for the micro-structure in ciliated organisms', J. Fluid. Mech. 55, p.1-23 (1972). In this article, it is described that the influence of cilia on fluid flow is modeled by representing the cilia as a collection of "Stokeslets" along their centerline, which can be viewed as point forces within the fluid. The movement of these Stokeslets in time is prescribed, and the resulting fluid flow can be calculated. Not only the flow due to a single cilium can be calculated, also that due to a collection of cilia covering a single wall with an infinite fluid layer on top, moving according to a metachronic wave. The approach of a preferred aspect of the present invention makes use of this to mimic the cilia- like fluid manipulation in micro -channels by covering the walls of the micro-channels with "artificial cilia" based on microscopic polymer actuator elements, i.e. polymer structures changing their shape and/or dimension in response to a certain external stimulus. In the following description, the microscopic actuator elements such as polymer actuator elements may also be referred to as actuators, e.g. polymer actuators or micro-polymer actuators, actuator elements, micro-polymer actuator elements, ciliary actuator elements or polymer actuator elements. It has to be noted that when any of these terms is used in the further description always the same microscopic actuator elements according to embodiments of the invention are meant.
The actuator elements comprise a host material and at least one component provided to the host material. According to embodiments of the invention, the host material may, for example, be based on polymer materials. Suitable materials that may be used as a host material may be found in the book "Electroactive Polymer (EAP) Actuators as Artificial Muscles", ed. Bar-Cohen, SPIE Press, 2004. However, also other materials may be used as a host material for the actuator elements. The materials that may be used as a host material to form actuator elements according to embodiments of the present invention should be such that the formed actuator elements have the following characteristics: - the actuator elements should be compliant, i.e. not stiff, the actuator elements should be tough, not brittle, the actuator elements should respond to a certain stimulus such as e.g. light, an electric field, a magnetic field, etc. by bending or changing shape, and the actuator elements should be easy to process by means of relatively cheap processes.
Depending on the type of actuation stimulus, the materials used to form the actuator elements may have to be functionalized. Considering the first, second and fourth characteristic of the above summarized list, polymers are preferred for at least a part of the actuators, e.g. for the host material. Most types of polymers can be used according to embodiments of the present invention, except for very brittle polymers such as e.g. polystyrene which are not very suitable to use with the present invention. In some cases, for example in case of electrostatic or magnetic actuation (see further), metals may be used to form the actuator elements or may be part of the actuator elements, e.g. in Ionomeric Polymer-Metal composites (IPMC). According to embodiments of the invention, all suitable materials, i.e. materials that are able to change shape by, for example, mechanically deforming as a response to an external stimulus, may be used as a host material. Traditional materials that show this mechanical response, and that may be applied to form actuator elements for use with embodiments of the present invention, may be electro-active piezoelectric ceramics such as, for example, barium titanate, quartz or lead zirconate titanate (PZT). These materials may respond to an applied external stimulus, such as for example an applied electric field, by expanding. However, an important drawback of electro-active ceramics is that they are brittle, i.e. they fracture quite easily. Furthermore, the processing technologies for electro- active ceramics are rather expensive and cannot be scaled up to large surface areas.
Therefore, electro-active piezoelectric ceramics may only be suitable in a limited number of cases.
A more recently explored class of responsive materials is that of shape memory alloys (SMA's). These are metals that demonstrate the ability to return to a memorized shape or size when they are heated above a certain temperature. The stimulus here is thus change in temperature. Generally, those metals can be deformed at low temperature and will return to their original shape upon exposure to a high temperature, by virtue of a phase transformation that happens at a critical temperature. Examples of such SMA's may be NiTi or copper-aluminium-based alloys (e.g. CuZnAl and CuAl). Also SMA's have some drawbacks and thus limitations in the number of cases in which these materials may be used to form actuator elements. The alloys are relatively expensive to manufacture and machine, and large surface area processing is not easy to do. Also, most SMA's have poor fatigue properties, which means that after a limited number of loading cycles, the material may fail. Other materials that can be used with embodiments of the present invention include all forms of Electroactive Polymers (EAPs). The may be classified very generally into two classes: ionic and electronic. Electronically activated EAPs include any of electrostrictive (e.g. electrostrictive graft elastomers), electrostatic (dielectric), piezoelectric, magnetic, electrovisco-elastic, liquid crystal elastomer, and ferroelectric actuated polymers. Ionic EAPs include gels such as ionic polymer gels, Ionomeric Polymer-Metal Composites (IPMC), conductive polymers and carbon nanotubes. The materials may exhibit conductive or photonic properties, or be chemically activated, i.e. be non-electrically deformable. Any of the above EAPs can be made to bend with a significant curving response and can be used in the form, for example, of ciliary actuators. Because of the above, according to embodiments of the present invention, the host material of the actuator elements may be formed of, or include as a part of their construction, polymer materials. Polymer materials are, generally, tough instead of brittle, relatively cheap, elastic up to large strains (up to 10%) and offer perspective of being processable on large surface areas with simple processes. Actuator elements formed of materials which can respond to temperature changes, visible and UV light, water, molecules, electrostatic field, magnetic field, electric field, may be used according to embodiments of the invention. Suitable materials can be identified from the above book by Bar-Cohen. The basic idea of the invention which is based on artificial cilia manipulating fluids on a small scale is independent of the material the actuator means is formed of. However, for biomedical applications, for example, light- and magnetic actuation means may be preferred, considering possible interactions with the complex biological fluids that may occur using other materials to form the actuator elements. The actuator elements furthermore comprise at least one component which is provided to the host material. According to embodiments of the invention, and depending on the kind of stimuli to be applied, the at least one component may comprise one or more photochromic moiety, which may optionally comprise reactive groups, one or more mesogenic group which may optionally comprise reactive groups, a semiconductive material or monomers leading to a semiconductive polymer, an electrically conductive material e.g. in the form of electrically conductive films, particles and/or agglomerates, a magnetic material e.g. in the form of magnetic films, particles and/or agglomerates, the magnetic properties may e.g. be (super)paramagnetic or ferromagnetic, a combination of materials having polar and apolar nature which may optionally comprise reactive groups or a material comprising one or more ionic groups which may optionally comprise reactive groups and/or capable of forming hydrogen bonds.
The material used for forming the actuator elements 10, i.e. the host material provided with the at least one component may also be referred to as multiple-stimuli materials, e.g. two-stimuli materials. Fig. 4 to Fig. 6 illustrate examples of actuator elements 10 according to embodiments of the present invention. It has to be understood that these examples are only for the purpose of illustration and are not intended to limit the invention in any way.
In Fig. 4 a first example is illustrated. According to this example, the actuator elements 10 may comprise a host material 11, e.g. polymer material and a component 12 provided in or on the host material 11, e.g. polymer material in the form of a continuous layer. This layer may, for example, be a conductive or semiconductive layer or a magnetic layer. According to embodiments of the invention, the component 12 in the form of a continuous layer may be positioned at the top (upper drawing of Fig. 4) or at the bottom of the actuator element 10 (drawing in the middle of Fig. 4), or may be situated in the centre of the actuator element 10 (lower drawing of Fig. 4). The continuous layer may, for example, be deposited as a uniform layer. According to other embodiments, instead of a uniform layer, the continuous layer may also be patterned (not shown in the drawings) to increase the compliance and ease of deformation of the actuator elements 10. The material the continuous layer is formed of depends on the actuation mechanism that will be used. In case of, for example, magnetic actuation, the component 12 may be provided as a magnetic layer. The magnetic layer may, for example, be an electroplated permalloy, e.g. Ni-Fe and may, for example, have a thickness of between 0.1 μm and 10 μm.
In Fig. 5 other examples of actuator elements 10 are illustrated. According to these examples, the actuator elements 10 may comprise a host material 11, e.g. polymer material and a component 12 in the form of particles. The host material 11, e.g. polymer material may in that case function as a matrix in which the particles are dispersed. In case of a polymer host material, the particles may be added to the polymer in solution or may be added to monomers that, later on, then can be polymerized. In a subsequent step, the polymer may then be applied to the inner side of wall of a micro-channel by any suitable method, e.g. by a wet deposition technique such as e.g. spin-coating. The particles may, for example, be spherical, as is illustrated in the upper tow drawings in Fig. 5 or may be elongated, e.g. rod- shaped, as is illustrated in the lower drawing of Fig. 5. Rod-shaped particles may have an advantage of automatically being aligned by shear flow during the deposition process. The particles may be randomly arranged in the host material matrix, as is illustrated in the upper and lower drawing of Fig. 5 or they may be arranged or aligned in the host material matrix in a regular pattern, e.g. in rows, as is illustrated in the drawing in the middle of Fig. 5. In case of magnetic actuation, the component 12 may be provided in the host material 11, e.g. polymer material as magnetic particles. The magnetic particles may, for example, be ferro- or ferri-magnetic particles, or (super)paramagnetic particles, comprising, for example, elements such as cobalt, nickel, iron, ferrites. According to embodiments of the invention, the magnetic particles may be superparamagnetic particles, i.e. they do not have a remanent magnetic field when an applied magnetic field has been switched off, especially when elastic recovery of the polymer is slow compared to magnetic field modulation. Long off-time of the magnetic field may save power consumption. Fig. 6 illustrates another example of an actuator element 10 according to embodiments of the invention. According to this example, the actuator element 10 may comprise different segments. Segments formed by the host material 11, e.g. polymer material may alternate with segments formed by the at least one component 12. The segments of the at least one component 12 may act as hinges (see further) when the actuator element 10 is being actuated. These hinge-like segments are geometrically distributed within the host material 11.
According to embodiments of the invention, the actuator elements 10 may be polymer MEMS (micro-electromechanical system) which may, for example, have a rod-like shape or a beam-like shape.
Fig. 7 schematically illustrates a micro-fluidic system 100 according to an embodiment of the invention. A plurality of actuator elements 10 is arranged on an inner side 13 of a wall 14 of a micro-channel 15. A cross-section of a micro-channel 15 is schematically depicted. In the example given, a plurality of straight actuator elements 10 is provided onto the inner side 13 of the wall 14 of the micro-channel 15. Upon actuation, i.e. under the action of external stimuli the actuator elements 10 can move back and forth and can change their shape (see further). According to embodiments of the invention, the actuator elements 10 may be arranged in one or more rows. As an example only, the actuator elements 10 may be arranged in two rows of actuator elements 10, i.e. a first row of actuator elements 10 on a first position at the inner side 13 of the wall 14 and a second row of actuator elements 10 at a second position of the inner side 13 of the wall 14, the first and second position being substantially opposite to each other. In other embodiments of the invention, the actuator elements 10 may also be arranged in a plurality of rows of actuator elements 10 which may be arranged to form, for example, a two-dimensional array. In still further embodiments, the actuator elements 10 may be randomly positioned at the inner side 13 of the wall 14 of the micro-channel 15.
For the purpose of actuation of the actuator elements 10, the micro-fluidic system 100 furthermore comprises stimulus application means 16, which is schematically illustrated in Fig. 7 and which is adapted for applying a combination of at least a first and a second stimulus to the plurality of ciliary actuator elements 10. The first stimulus is for actuating one of the host material or one of the at least one component provided to the host material, and the second stimulus is for actuating one of the host material or one of the at least one component provided to the host material. The first and second stimuli are for actuating different materials. The stimulus application means may be adapted for applying first and second stimuli so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements 10. The asymmetric motion may be a geometrical or functional asymmetric motion. According to embodiments of the invention, the stimulus application means 16 may be adapted for first applying the first stimulus and subsequently applying the second stimulus. According to these embodiments, the first and second stimulus may be different stimuli or may be a same stimulus. In this latter case, for example, according to embodiments of the invention, the stimulus may e.g. be light and the first and second light beams may have different wavelength. According to other embodiments, the stimulus may be application of a magnetic field and the first and second magnetic field may have a different rotation rate. According to other embodiments of the invention, the stimulus application means 16 may be adapted for simultaneously applying the first stimulus and the second stimulus. According to embodiments of the invention, the stimulus application means 16 may, for example, comprise a combination of at least two actuation means chosen from the list of magnetic actuation means, photonic or light induced actuation means, electrostatic actuation means or thermal actuation means. According to particular embodiments of the invention, the stimulus application means 16 may comprise at least two different actuation means for applying two different stimuli, or may comprise a same actuation means for at least twice applying a same stimulus.
Fig. 8 illustrates an example of asymmetric motion of a ciliary actuator element 10 obtained by using a stimulus application means 16 adapted according to embodiments of the present invention. The ciliary actuator element 10 is provided on the inner side 13 of a wall 14 of a microchannel 15 (see Fig. 8a). According to this example, the stimulus application means 16 may comprise a magnetic actuation means 17 and a light induced actuation means 18. The actuation of the actuator elements 10 is, according to the present example, initially effected magnetically, resulting in a bending of the actuator element 10 around a 'hinge' (indicated with reference number 19 in Fig. 8b) situated at a bottom of the actuator element 10 (see Fig. 8b and 8c), followed by light induced actuation, also referred to as photonic actuation, resulting in an additional second kink (indicated with reference number 20 in Fig. 8d) in the actuator element 10. In the present example, recovery may be realized through relaxation (see Fig. 8e and 8f) and/or optionally using a second light induced actuation step, possibly of different wavelength than the first light induced actuation step (see Fig 8g).
According to the present example, asymmetric motion of the actuator elements 10 may be achieved by providing the at least one component 12 as hinge-like segments 19, 20 that are geometrically distributed within the host material 11, as schematically shown in Fig. 8, and as already illustrated and discussed with respect to Fig. 6. However, the realization of asymmetric actuation does not depend on a geometrical hinge-like design as illustrated in Fig. 6 and Fig. 8. Alternatively, the at least one component 12 may be in the form of particles (see Fig. 5) which may be distributed homogeneously within the host material 11. In the case of magnetic and photonic actuation, the dispersed particles, which may be magnetic particles and photochromic moieties, will respond to the applied external stimuli, in the example given magnetic and photonic actuation, throughout the entire material. Obviously, also geometrical intermediate designs can be envisioned and are also part of the present invention.
According to the present example, the intra-molecular geometry of the actuator element 10 is thus independently changed by a combination of first and second, e.g. magnetic and photonic, actuation as separate stimuli.
The magnetic actuation can be realized through the incorporation of dispersed magnetic particles, or the incorporation of concentrated regions of magnetic elements, for example through the use of magnetic films deposited on the matrix or incorporated within the matrix. Of course, combinations thereof can also be envisioned. The magnetic particles or films may exhibit ferromagnetism, or (super)paramagnetism, depending on the desired actuation characteristics. In practice, the magnetic particles will usually be stabilized via a tailored stabilizer, for example (block-co)polymers or ionic groups.
Photonic actuation can be obtained by using a photoresponsive material as a component 12 provided to, e.g. in or on, the host material. The photoresponsive material may comprise chromophores which lead to photochromism. Photochromism is defined as a reversible phototransformation of a chemical species between two forms with different absorption spectra. During photo-isomerisation, also other properties may change, such as e.g. the refractive index, dielectric constant and geometrical structure. Particular non- limitative examples of materials that may be used with photonic actuation according to embodiments of the invention may be azobenzenes (see Fig. 9(a)), spirobenzopyranes (see Fig. 9(b)), stilbenes (see Fig. 9(c)), α-hydrazono-β-ketoesters (see Fig. 9(d)), and cinnamates. For illustration purposes, Fig. 10 shows typical absorption spectra for the two photo-isomers of an azobenzene compound (see Fig. 9(a)), in its respective E (trans) and Z (cis) state. The energetically most stable conformation, the E-state, can be converted to its corresponding Z-state using UV light. The resulting Z-state can be converted back using longer wavelength light (e.g. visible light), but also using for example a thermal driving force. The latter is usually already governed by ambient temperatures. Consequently, the Z- state of these materials is usually not stable over time, even in the dark, and can relax back in hours to seconds, even milliseconds.
There are various ways to incorporate such photochromic materials in a carrier matrix, i.e. in the host material 11, e.g. polymer material. For example, the chromophores may be incorporated in the host material 11 via reactive groups, e.g. acrylate groups, epoxides, in a polymer matrix, such as a polymer network. By making use of the mesomorphic properties, the absorption can be controlled even further using polarized light for the photonic actuation. The effectiveness will strongly depend on the morphology of the host system.
Fig. 11 illustrates an example of a system of components 12 that can be incorporated in the host material 11 to form an actuator element according to an embodiments of the invention and suitable to be used with a combination of magnetic and photonic actuation. A system comprising one or more acrylate monomers containing azobenzene moieties, one or more non-photochromic groups containing acrylates, stabilized superparamagnetic particles (e.g. Fe 3 O 4 nanoparticles with a diameter of about 10 nm and dispersed in a carrier fluid, e.g. N-methylpyrrolidon, on 50% w/w basis), a photoinitiator (e.g. Irgacure 651 or Irgacure 819) or thermal initiator (e.g. AIBN (2,2'-Azobisisobutyronitrile)), were thermally or photochemically polymerized in-situ, resulting in a micron-sized thin film. In this particular example, no use was made of the mesogenic order, by enforcing a multi- domain structure of the liquid crystalline network. Selective control of the actuation direction was achieved by introducing an absorption gradient over the film, caused by the presence of the magnetic particles. Snapshots of the actuation process of a film produced by this example are shown in Fig. 12. The polymeric film comprising superparamagnetic particles and azobenzene moieties and forming an actuator element 10 according to an embodiment of the present invention, had a thickness of 5 μm. The actuator element 10 is fixed in a clamp 21 and positioned near a magnetic pole, which acts as a magnetic actuation means 17. Furthermore, a light source was provided (not shown in the Figure). Fig. 12(a) shows the initial situation. Both the magnetic field and the light source are switched off. For clarity issues, the shape of the actuator element 10 is indicated by dashed lines. After the magnetic field was switched on, the actuator element 10 is attracted to the magnetic pole 15 (see Fig. 12(b)). When the magnetic field was turned off, the actuator element 10 moved away from the magnetic pole 15 (see Fig. 12(c)). While keeping the magnetic field off, the light source was switched on to illuminate part of the actuator element 10. As can be seen from Fig. 12(d) to Fig. 12(f) the illuminated part 22 of the actuator element 10 deformed.
In another example, the liquid crystalline carrier was replaced by an intrinsically isotropic polymeric matrix, consisting of a low Young's modulus polyetherurethaneacrylate with variable molecular weight. Again, an absorption gradient was introduced by the presence of magnetic particles. Alternatively, a (stacked) magnetic film may be used.
In yet another example, a film is envisioned by polymerizing a mixture consisting of an apolar monomer (e.g. hexanediol diacrylate), a polar monomer (e.g. 3- hydroxypropyl acrylate), a photoinitiator (e.g. Irgacure 651), and optionally a light absorbing component with a preferential absorption in the wavelength region similar to the excitation wavelength region of the employed photoinitiator (e.g. Tinuvin 928), in the presence of (ferro- or para-)magnetic particles.
It has to be noted that the present invention is not limited to the stimulation or actuation of actuator elements as described above, i.e. to a combination of magnetic actuation and photonic actuation. Other combinations of first and second stimuli, such as for example but not limited to, magnetic and electrostatic actuation, electrostatic and photonic actuation, magnetic and thermal actuation, etc. can also be envisioned. According to still further embodiments, also a same actuation may be performed at least twice. Summarized it can be said that the actuator elements 10 according to embodiments of the invention may comprise:
A host material, for instance comprising at least one polymer component:
- A polymer host may be formed in-situ from a monomer or mixture of different monomers. - An optional initiator, allowing for the in-situ formation of the host, using either thermal initiation including room temperature conditions, photonic actuation of variable wavelengths, or combinations thereof.
- Optional additives, such as sensitizers, radical scavengers and inhibitors, UV-stabilizers, absorbing species such as colorants and pigments, agents capable of inducing helical twisting power, transfer agents, stabilizers, buffering components, complexation agents of any kind.
Depending on the chosen stimulus or actuation means, one or more of the following components:
- A material containing one or more photochromic moieties, optionally also containing reactive groups.
- A material containing one or more mesogenic groups, optionally also containing reactive groups, such that they exhibit anisotropic thermal expansion coefficients.
- A semi-conductive material, such as semi-conductive polymers, or monomers potentially leading to the formation of semi-conductive polymers. - An electrically conductive component that may be present in the form of incorporated electrically conductive films, particles and/or agglomerates.
- A magnetic component that may be present in the form of incorporated magnetic films, particles and/or agglomerates. The magnetic properties can, for example, be (super)paramagnetic or ferromagnetic.
- A combination of materials of polar and apolar nature, optionally also containing reactive groups.
- A material containing one or more ionic groups, optionally also containing reactive groups and/or capable of forming hydrogen bonds. A micro-fluidic system according to embodiments of the invention may have at least one of the following advantages:
Realization and control of geometrical or functional asymmetric actuation in actuator elements 10, e.g. polymeric micro-actuators.
Additional degrees of freedom for realization of the geometrical or functional asymmetric actuation through morphological control, i.e. use of homogeneously distributed components 12, which may be in the form of layers, particles or geometrically differently positioned hinge-like segments, in a host material 12.
Unprecedented control and actual demonstration of actuating principles using combinations of a large variety of external stimuli. - Realization and control of complex flow patterns for micro-fluidic applications, which may be of high importance for, for example, effective displacement of liquids in micro-channels.
In a second aspect of the invention, a method is provided for controlling or manipulating a fluid flow through a micro-channel 15 of a micro-fluidic system 100, the micro-channel 15 having a wall 13 with an inner side 14 being provided with a plurality of ciliary actuator elements 10, each ciliary actuator element 10 comprising a host material 11 and at least one component 12 provided to the host material 11, the method comprising: applying a first stimulus to the ciliary actuator elements 10 for actuating one of the host material 11 or one of the at least one component 12, and - applying a second stimulus to the ciliary actuator elements 10 for actuating one of the host material 11 or one of the at least one component 12, the first and second stimuli being for actuating different materials.
Applying a first stimulus and applying a second stimulus may be performed so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements 10. The asymmetric motion can be an asymmetric geometrical, asymmetric temporal or asymmetric functional motion. With asymmetric geometrical motion is meant that the asymmetry in motion may be achieved by an asymmetric geometrical design. By asymmetric temporal motion is meant temporal asymmetry in applying the stimuli, or by building in asymmetry in functionality. In this case, the times for the forward and the backward stroke to be completed are different. Asymmetric functional motion implies that actuator material properties, in particular the stiffness, are different in the forward and the backward stroke.
It is an advantage of a method according to embodiments of the invention that it enables realization and control of complex flow patterns within e.g. microchannels of diagnostic devices, which may be of high importance for effective displacement of fluids through the microchannels.
Applying a first stimulus and applying a second stimulus may be performed by means of magnetic actuation, photonic or light induced actuation, electrostatic actuation or thermal actuation. According to embodiments of the invention, applying a second stimulus may be performed after the first stimulus has been applied. The first stimulus and second stimulus may be different or may be the same. In the latter case, for example, according to embodiments of the invention, the stimulus may e.g. be light and the first and second light beams may have different wavelength. According to other embodiments, the stimulus may be application of a magnetic field and the first and second magnetic field may have a different rotation rate. According to other embodiments, applying the first stimulus and applying the second stimulus may be performed simultaneously.
In a further aspect, the present invention also provides a system controller 25 for use in a micro-fluidic system 100 according to embodiments of the present invention for controlled driving a stimulus application means 16 of the micro-fluidic system 100. The system controller 25, which is schematically illustrated in Fig. 13, may comprise a control unit 26 for controlled driving of actuation means of the stimulus application means 16 for applying a first stimulus and a second stimulus to ciliary actuator elements 10 of the micro- fluidic system 100 so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements 10. The system controller 25 may include a computing device, e.g. microprocessor, for instance it may be a micro-controller. In particular, it may include a programmable controller, for instance a programmable digital logic device such as a Programmable Array Logic (PAL), a Programmable Logic Array, a Programmable Gate Array, especially a Field Programmable Gate Array (FPGA). The use of an FPGA allows subsequent programming of the micro-fluidic device 100, e.g. by downloading the required settings of the FPGA.
The method described above according to embodiments of the present invention may be implemented in a processing system 200 such as shown in Fig. 14. Fig. 14 shows one configuration of processing system 200 that includes at least one customizable or programmable processor 41 coupled to a memory subsystem 42 that includes at least one form of memory, e.g., RAM, ROM, and so forth. It is to be noted that the processor 41 or processors may be a general purpose, or a special purpose processor, and may be for inclusion in a device, e.g., a chip that has other components that perform other functions. Thus, one or more aspects of the method according to embodiments of the present invention can be implemented in digital electronic circuitry, or in computer hardware, firmware, software, or in combinations of them. The processing system may include a storage subsystem 43 that has at least one disk drive and/or CD-ROM drive and/or DVD drive. In some implementations, a display system, a keyboard, and a pointing device may be included as part of a user interface subsystem 44 to provide for a user to manually input information, such as parameter values. More elements such as network connections, interfaces to various devices, and so forth, may be included, but are not illustrated in Fig. 14. The various elements of the processing system 40 may be coupled in various ways, including via a bus subsystem 45 shown in Fig. 14 for simplicity as a single bus, but will be understood to those in the art to include a system of at least one bus. The memory of the memory subsystem 42 may at some time hold part or all (in either case shown as 46) of a set of instructions that when executed on the processing system 40 implement the steps of the method embodiments described herein.
The present invention also includes a computer program product which provides the functionality of any of the methods according to embodiments of the present invention when executed on a computing device. Such computer program product can be tangibly embodied in a carrier medium carrying machine-readable code for execution by a programmable processor. The present invention thus relates to a carrier medium carrying a computer program product that, when executed on computing means, provides instructions for executing any of the methods as described above. The term "carrier medium" refers to any medium that participates in providing instructions to a processor for execution. Such a medium may take many forms, including but not limited to, non-volatile media, and transmission media. Non-volatile media includes, for example, optical or magnetic disks, such as a storage device which is part of mass storage. Common forms of computer readable media include, a CD-ROM, a DVD, a flexible disk or floppy disk, a tape, a memory chip or cartridge or any other medium from which a computer can read. Various forms of computer readable media may be involved in carrying one or more sequences of one or more instructions to a processor for execution. The computer program product can also be transmitted via a carrier wave in a network, such as a LAN, a WAN or the Internet.
Transmission media can take the form of acoustic or light waves, such as those generated during radio wave and infrared data communications. Transmission media include coaxial cables, copper wire and fiber optics, including the wires that comprise a bus within a computer. It is to be understood that although preferred embodiments, specific constructions and configurations, as well as materials, have been discussed herein for devices according to the present invention, various changes or modifications in form and detail may be made without departing from the scope of this invention as defined by the appended claims.

Claims

CLAIMS:
1. A micro -fluidic system (100) comprising at least one micro-channel (15), wherein the micro-fluidic system (100) furthermore comprises: a plurality of ciliary actuator elements (10) in the micro-channel (15), each ciliary actuator element (10) comprising a host material (11) and at least one component (12) provided to the host material (11), and stimulus application means (16) adapted for applying a combination of at least a first and second stimulus to the plurality of ciliary actuator elements (10), the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
2. Micro-fluidic system (100) according to claim 1, wherein the stimulus application means is adapted for applying first and second stimuli so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements (10).
3. Micro-fluidic system (100) according to any of the previous claims, wherein the stimulus application means (16) comprises at least one actuation means chosen from the list of magnetic actuation means, photonic actuation means, electrostatic actuation means or thermal actuation means.
4. Micro-fluidic system (100) according to any of the previous claims, wherein the stimulus application means (16) is adapted such that the second stimulus is applied after the first stimulus has been applied.
5. Micro-fluidic system (100) according to any of claims 1 to 3, wherein stimulus application means (16) is adapted such that the first stimulus and second stimulus are applied simultaneously.
6. Micro-fluidic system (100) according to any of the previous claims, wherein the host material (11) comprises at least one polymer.
7. Micro-fluidic system (100) according to any of the previous claims, wherein the at least one component (12) comprises one or more photochromic moiety, one or more mesogenic group, a semiconductive material, an electrically conductive material, a magnetic material, a combination of materials having polar and apolar nature or a material comprising one or more ionic groups.
8. A method for the manufacturing of a micro-fluidic system (100), the micro- fluidic system (100) comprising at least one micro-channel (15), the method comprising: providing a plurality of ciliary actuator elements (10) attached to an inner side (13) of a wall (14) of the micro-channel (15), each ciliary actuator element (10) comprising a host material (11) and at least one component (12) provided to the host material (11), and - providing stimulus application means (16) adapted for applying a combination of at least a first and second stimulus to the plurality of ciliary actuator elements (10), the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
9. A method for controlling or manipulating a fluid flow through a micro-channel (15) of a micro-fluidic system (100), the micro-channel (15) being provided with a plurality of ciliary actuator elements (10) each comprising a host material (11) and at least one component (12) provided to the host material (11), the method comprising: - applying a first stimulus to the ciliary actuator elements (10) for actuating one of the host material (11) or one of the at least one component (12), and applying a second stimulus to the ciliary actuator elements (10) for actuating one of the host material (11) or one of the at least one component (12), the first and second stimuli being for actuating different materials.
10. A method according to claim 9, wherein applying a first stimulus and applying a second stimulus is performed so as to cause an asymmetric motion of each of the plurality of ciliary actuator elements (10).
11. Method according to any of claims 9 or 10, wherein applying a first stimulus is performed by means of magnetic actuation, photonic actuation, electrostatic actuation or thermal actuation.
12. Method according to any of claims 9 to 11, wherein applying a second stimulus is performed by means of magnetic actuation, photonic actuation, electrostatic actuation or thermal actuation.
13. Method according to any of claims 9 to 12, wherein applying a second stimulus is performed after the first stimulus has been applied.
14. Method according to any of claims 9 to 12, wherein applying a first stimulus and applying a second stimulus are performed simultaneously.
15. A controller (25) for controlled driving a stimulus application means (16) of a micro-fluidic system (100) comprising a plurality of ciliary actuator elements (10) each comprising a host material (11) and at least one component (12) provided to the host material (11), the controller (25) comprising a control unit (26) for controlled driving of actuation means of the stimulus application means (16) so as to apply a first stimulus and a second stimulus to the ciliary actuator elements (10) of the micro-fluidic system (100), the first stimulus being for actuating one of the host material or one of the at least one component, and the second stimulus being for actuating one of the host material or one of the at least one component, the first and second stimuli being for actuating different materials.
PCT/IB2009/052371 2008-06-13 2009-06-04 Micro-fluidic systems based on actuator elements WO2009150585A1 (en)

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WO2006087655A1 (en) * 2005-02-21 2006-08-24 Koninklijke Philips Electronics N.V. Micro-fluidic systems based on actuator elements
WO2008010181A2 (en) * 2006-07-17 2008-01-24 Koninklijke Philips Electronics N.V. Micro-fluidic system

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