WO2008139378A1

WO2008139378A1 - Pulse driving of actuator elements for fluid actuation

Info

Publication number: WO2008139378A1
Application number: PCT/IB2008/051795
Authority: WO
Inventors: Murray F. Gillies; Marc W. G. Ponjee; Mark T. Johnson; Jacob M. J. Den Toonder; Judith M. De Goede; Tim Dekker
Original assignee: Koninklijke Philips Electronics N.V.
Priority date: 2007-05-11
Filing date: 2008-05-08
Publication date: 2008-11-20

Abstract

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: at least one ciliary actuator element attached to said inner side of said wall, the at least one ciliary actuator element having an original shape and an orientation, and a stimulus applicator for applying an electrical field to said at least one ciliary actuator element so as to cause a change in its shape and/or orientation. The stimulus applicator is adapted such that at least part of the applied electrical field comprises stimuli at a frequency above 50 Hz, preferably above 500 Hz. The present invention also provides a corresponding method for controlling a fluid flow through a micro-channel of a micro-fluidic system and a controller for controlling such fluid flow.

Description

Pulse driving of actuator elements for fluid actuation

FIELD OF THE INVENTION

The present invention relates to micro-fluidic systems, to a method for controlling or manipulating a fluid flow through micro-channels of such a micro-fluidic system, and to a controller for controlling or manipulating a fluid flow through micro- channels of such a micro-fluidic system. More particularly, the present invention relates to controlled actuation of actuator elements. The micro-fluidic systems may be used in biotechno logical and pharmaceutical applications and in micro-channel cooling systems in microelectronics applications. Micro-fluidic systems according to the present invention are compact, cheap and easy to process. The driving of the fluidic systems according to the present invention avoids electrolysis of the controlled or manipulated fluid.

BACKGROUND OF THE INVENTION

Microfluidics 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, which can process microliter and nano liter volumes of fluid and conduct highly sensitive analytical measurements. The fabrication techniques used to construct microfluidic 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, microfluidic technologies enable the fabrication of highly integrated devices for performing several different functions on a same substrate chip.

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. Microfluidics is a critical component in, amongst others, gene chip and protein chip development efforts. Biochips for (bio)chemical analysis, such as molecular diagnostics, will become an important tool for a variety of clinical, forensic and food applications. Such biochips incorporate a variety of laboratory steps in one desktop machine.

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 microfluidic 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, electrical actuation (such as (di)electrophoresis and electroosmosis), capillary movement, pressure-driven schemes e.g. via MEMS, micro-fabricated mechanical valves and pumps, inkjet-type pumps, electro-kinetically controlled flows, thermal gradients and surface-acoustic waves.

Recently, also polymer composite structures have been suggested for use as fluid actuators, as described in WO 2006/087655. In this document, the use of electrostatically actuated polymer composite structures (PoIyMEMS) is described for the manipulation of biological fluids. A schematic cross-section of an embodiment of such a structure 10 can be seen in Fig. 1. The structure 10 comprises a first electrode 11, also called under-electrode, covered by an insulator 12 (e.g. SiO2, acrylate film), and an actuator element 16 consisting of a double layer, i.e. a second electrode 14 (for example chromium), and an insulating layer 13 (e.g. polymide, acrylate). The actuator element 16 is structured and freed, e.g. by photo-lithography and sacrificial layer etching, from the underlying substrate 15 and the layers applied thereto. Due to the internal stress caused by the double layer, the actuator element 16 curls upward, away from the substrate 15. With electric actuation, upon applying a voltage difference between the two electrodes 11, 14, this actuator element 16 can overcome the force caused by the internal stress in the actuator element material and un-roll. When the voltage is removed the actuator element 16 rolls-up again to its original position. The actuator elements 16 can be between 15 and 100 um in length. The actuator elements 16 can be actuated at frequencies of 1-1000 Hz, even in the presence of a fluid.. Such structures 10 can also be used to mix fluids efficiently.

There are many MEMS devices that are actuated by voltages. A common problem with applying dc voltages is that insulators experience a charge build-up which can later cause problems such as sticking of the actuator element onto the underlying substrate. This is usually avoided by using non-DC electrical fields for driving, rather than DC fields. The frequency of the non-DC field is, however, not important as the reason for using non-DC fields is only to avoid charging of the insulator. A non-DC type of driving can also be used for driving the actuator elements 16. This is illustrated in Fig. 2 (together with a schematic illustration the state of the actuator element 16). Initially a voltage of -80 V is applied for 1 s, this results in the actuator element 16 rolling out. The voltage is then increased to zero and the actuator element 16 rolls back-up. The next actuation uses the inverted voltage (+80 V) and again the actuator element 16 rolls out. So long as an even number of actuation events occur then this way of driving, which is in fact a balanced DC voltage driving, results in no charging of the insulator layer 13 of the actuator element 16. A problem with electrostatic actuation is that electrolysis can quickly occur in bio-liquids, as these are often water based. The voltages needed to drive the actuator elements 16 depend on its design but typically these are tens of volts, whereas in practice electrolysis typically occurs for voltages >1.2 V. Due to the fact that one of the electrodes 14 is in direct contact with the fluid (which is usually water) then, if the insulating material 12 (e.g. SiO₂ under-layer) on top of the other electrode 11 is not a perfect insulator, electrolysis will occur and gas will be released. Electrolysis causes irreparable damage to the actuator elements 16, with as a result corrosion of the electrodes 14 and strong pH variations that can degrade or de-nature the biological sample.

Even if the insulating layer 12 is a perfect insulator then it is liable to charging if an unbalanced dc voltage is applied to the sample. This causes sticking of the actuator elements 16 to the substrate 15.

When applying a DC balanced driving as described in the prior art to actuator elements 16 in an aqueous liquid there was no movement of the actuator elements 16. The explanation might be that when a voltage is applied to the structures in the presence of a conducting liquid, as will be the case for the application of actuating biological fluids, then the ionic species in the fluid move rapidly to the electrodes. There they build up a layer of opposite charge that compensates for the externally applied field. In the most extreme case the ions completely compensate the applied field, such that the actuators do not respond at all to the applied voltage.

SUMMARY OF THE INVENTION

It is an object of the present invention to provide a good micro-fluidic system and method of controlling a fluid flow through such a system. The above objective is accomplished by a device and method according to the present invention.

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.

In a first aspect, 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: - at least one ciliary actuator element, preferably a plurality of ciliary actuator elements, attached to said inner side of said wall, the at least one ciliary actuator element, preferably each ciliary actuator element, having an original shape and an orientation, and a stimulus applicator for applying a force field, e.g. an electrical field, to said at least one ciliary actuator element, e.g. to said plurality of ciliary actuator elements, so as to cause a change in its or their shape and/or orientation, wherein the stimulus applicator is adapted such that at least part of the force field comprises stimuli, e.g. electrical stimuli, at a frequency above 50 Hz, preferably between 50 Hz and 50 kHz, still more preferred between 500 Hz and 50 kHz and yet more preferred between 1 kHz and 50 kHz. The Original shape and/or orientation' is the shape and/or orientation taken by the at least one ciliary actuator when no force field is applied by means of the stimulus applicator to the at least one ciliary actuator elements. With 'at least part of the force field comprising stimuli at a frequency above 50 Hz' is meant that a multi-phase force field may be applied, whereby at least one of the phases comprises stimuli at a frequency above 50 Hz. For example, during a first phase, one or more pulses at a frequency above 50 Hz can be given, after which, during a second phase, a signal with a lower holding frequency can be applied.

Application of stimuli to the one or more ciliary actuator elements provides a way to locally manipulate the flow of complex fluids in a micro-fluidic system. The actuator elements or elements may be driven or addressed individually or in groups to achieve specific ways of fluid flow.

Applying such high-frequency actuation has the advantage that, in case of electrical actuation, it avoids electrolysis of the fluid present in the micro-fluidic system. Furthermore, the high frequency also immobilizes ions in the fluid, and thus avoids that the ionic species in the fluid build up a layer of opposite charge at the electrodes, thus compensating for the externally applied field and preventing the actuator elements from moving.

In a micro-fluidic system according to embodiments of the present invention the stimulus applicator may be adapted for applying a multi-phase force field, at least two of the phases having a different force field amplitude and/or force field frequency, and wherein at least one of the phases comprises stimuli at a frequency above 50 Hz. The multi-phase force field may for example be a dual-phase force field or a three-phase force field. Preferably, the multi-phase force field may have higher amplitudes during earlier phases than during further or later phases. For example, the multi-phase force field may preferably have a higher amplitude during a first phase than the force field during a second phase, the first phase coming in time before the second phase. The multi-phase force field, if having at least three phases, the first phase coming in time before the second phase, and the second phase coming in time before the third phase, may preferably have a higher amplitude during a second phase than during a third phase. This is advantageous as it reduces the power consumption of the system and also negative effects due to electromigration. The force field during a first phase may be sufficient to cause a change in shape and/or orientation of the at least one ciliary actuator element, e.g. may cause roll-out thereof. The force field during a second phase may be lower in amplitude than the force field during the first phase, but nevertheless sufficient to maintain the ciliary actuator element in its changed shape and/or orientation.

In a micro-fluidic system according to embodiments of the present invention, wherein the force field is at least a three-phase force field, the force field during the third phase may have an amplitude below the electrical hysteresis voltage of the at least one actuator element. In a micro-fluidic system according to embodiments of the present invention, wherein the force field is a periodic field, e.g. a periodic electrical field, the number of pulses of one period of the force field may be even. This avoids internal charging of an insulator layer part of the ciliary actuator element. Even if one pulse with a particular time duration, e.g. 1 ms, is enough for changing the shape and/or orientation of an actuator element, e.g. for obtaining roll-out of the actuator element, a second pulse of equal time duration but opposite voltage should preferably always be given to obtain a net zero voltage load. In case of a multi-phase force field, the number of pulses of each phase of the force field may be even. This provides the same advantage. In a micro-fluidic system according to embodiments of the present invention, the at least one ciliary actuator element may be a polymer actuator element. The at least one polymer actuator element may comprise polymer MEMS. 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. Therefore, they are particularly suitable for being used to form actuator elements according to the present invention.

In accordance with embodiments of the present invention, the stimulus applicator for applying a force field to the at least one ciliary actuator element may be an electric field generating means (e.g. a current source or a voltage source). The stimulus applicator may be adapted for providing an electrical force field. For example, a voltage may be applied to the actuator element, or a voltage difference may be applied between the actuator element and a second electrode. Embodiments of the present invention may preferably be used in cases when the electrical field applied not only actuates the at least one ciliary actuator element so as to change shape and/or orientation, but also moves ions in the actuated fluid.

In case of electrical actuation, the at least one ciliary actuator element may be in contact with the fluid, e.g. water. A second electrode may be provided, which is insulated from the fluid. The at least one actuator element in contact with the fluid may be held at a common voltage and actuating voltages may be applied to the at least one second electrode insulated from the fluid. In case of a plurality of actuator elements being provided, different sets of actuator elements can then be modulated with different voltages.

In embodiments of the present invention, the voltages applied for actuation of the at least one actuator element can have an amplitude above the threshold for electrolysis of the fluid to be actuated. For example in case of aqueous fluids, the applied voltage can have an amplitude above 1.2 Volts.

In embodiment of the present invention, electrical fields, e.g. voltages, may be applied via Large- Area Electronics (LAE). Large-Area Electronics are electronic devices fabricated on a rigid substrate such as glass or on a flexible material such as a roll of flexible substrate, e.g. plastic or metal foil. Thin film transistors can be formed by first depositing amorphous silicon and then using doping and other semiconductor processing techniques to form the transistors. The properties of the amorphous silicon can be improved by re- crystallization, e.g. laser re-crystallization. This can form polycrystalline silicon with improved properties e.g. by Low Temperature Poly-crystalline Silicon (LTPS) processing. Other technologies can be used such as those based on amorphous silicon (aSi:H), or micro- or nanocrystalline silicon that can be made using a process similar to aSI:H but with altered process conditions to generate micro- or nano-sized particles. Also other semiconductor systems may be used if these are adaptable to similar low cost processing. For example, in low temperature poly-crystalline silicon (LTPS) processing, amorphous silicon is deposited onto a substrate, preferably a transparent substrate such as made from glass, and lasers, or other low temperature energy sources, are used to crystallize the amorphous silicon into a more conductive state known as poly-crystalline silicon (p-Si). This poly-crystalline silicon layer can be patterned through photolithography to make a thin- film transistor (TFT) plane. Accordingly, the present invention includes within its scope the use of amorphous, microcrystalline, nanocrystalline or polycrystalline semiconductor layers, e.g. based on silicon, whereby at least a part of the electronics does not make use of monocrystalline semiconductor materials, e.g. monocrystalline silicon. An alternative approach is to use polymeric semiconductor materials that can be deposited by other techniques, e.g. sililar to inkjet printing. Large electronic circuits made with thin- film transistors and other devices can be easily patterned onto such large substrates, which can be up to a few meters wide and many meters long. Some of the devices can be patterned directly, much like an inkjet printer deposits ink. For most semiconductors, however, the devices must be patterned using photolithography techniques. The at least one ciliary actuator element may in particular be an electroactive polymer actuator element. The electroactive polymer actuator element may comprise a polymer gel or a Ionomeric Polymer-Metal Composite (IPMC).

In a micro-fluidic system according to embodiments of the present invention, the plurality of ciliary actuator elements may be arranged in a first and a second row, said first row of actuator elements being positioned at a first position of said inner side of said wall and said second row of ciliary actuator elements being positioned at a second position of said inner side of said wall, said first position and said second position being substantially opposite to each other, e.g. a bottom side and a top side of the micro-channel.

The plurality of ciliary actuator elements may be arranged in a plurality of rows of ciliary actuator elements which are arranged to form a two-dimensional array.

Alternatively, the plurality of ciliary actuator elements may be randomly arranged at the inner side of the wall.

A micro-fluidic system of embodiments of the present invention may be used in biotechnological, pharmaceutical, electrical or electronic applications. In a second aspect, the present invention provides a method for controlling a fluid flow through a micro-channel of a micro-fluidic system, the micro-channel having a wall with an inner side provided with at least one ciliary actuator element, the at least one ciliary actuator element having an original shape and an orientation. With Original shape and/or orientation' is meant the shape and/or orientation taken by the at least one ciliary actuator when no force field is applied to the at least one ciliary actuator elements for actuating it. The method comprises applying a force field to said at least one ciliary actuator element so as to cause a change in its shape and/or orientation, wherein at least part of the force field comprises stimuli at a frequency above 50 Hz, preferably between 50 Hz and 50 kHZ, more preferred between 500 Hz and 50 kHz, and still more preferred between 1 kHz and 50 kHz.

Applying a force field may comprise applying a multi-phase force field, at least two of the phases having a different force field amplitude and/or force field frequency, wherein at least one of the phases comprises stimuli at a frequency above 50 Hz. In particular the multi-phase force field may be a dual-phase force field or a three-phase force field. Applying a multi-phase force field may comprise applying a force field which during an earlier phase has a higher amplitude than during a later phase. The force field during a first phase may for example have a higher amplitude than the force field during a second phase. In particular for electrical actuation, this may be advantageous in terms of power consumption. In case of a three-phase actuation, reducing the amplitude of the third phase may be advantageous with respect to pumping efficiency in the micro-fluidic system.

Applying a force field may comprise applying a periodic force field in which the number of pulses of one period of the force field is even. Also, in case of a multi-phase actuation, the number of pulses of each phase of the force field are preferably even. In accordance with embodiments of the present invention, applying a force field to said at least one ciliary actuator element may be performed by applying an electric field.

In a third aspect, the present invention provides a controller for controlling a fluid flow through a micro-channel of a micro-fluidic system, the micro-channel having a wall with an inner side provided with at least one ciliary actuator element, the at least one ciliary actuator element having a shape and an orientation. The controller comprises a control unit for controlling amplitude and frequency of a force field to be applied to the at least one ciliary actuator element so as to cause a change in its shape and/or orientation, the control unit being adapted to provide a force field, wherein at least part of the force field comprises stimuli at a frequency above 50 Hz, preferably between 50 Hz and 50 kHz, more preferred between 500 Hz and 50 kHz, still more preferred between 1 kHz and 50 kHz.

The control unit may be adapted for controlling application of a multi-phase force field, at least two of the phases having a different force field amplitude and/or force field frequency, and wherein at least one of the phases comprises stimuli at a frequency above 50 Hz, preferably above 500 Hz. The multi-phase force field may for example be a dual-phase force field or a three-phase force field.

The control unit may be adapted to control application of a multi-phase force field which during a first phase has a higher amplitude than during a second phase. This is advantageous in terms of power consumption, avoiding dielectric charging and breakdown and any electrolysis which may occur via leakage currents.

The control unit may be adapted to control application of a periodic force field so that the number of pulses of one period of the force field is even. In case of multi-phase actuation, the control unit may be adapted to control application of the force field so that the number of pulses of each phase of the force field is even. This avoids internal charging of an insulator layer part of the at least one ciliary actuator element. Even if one pulse with a particular time duration, e.g. 1 ms, is enough for changing the shape and/or orientation of an actuator element, e.g. for obtaining roll-out thereof, a second pulse of equal time duration but opposite voltage should preferably always be given to obtain a net zero voltage load. 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.

BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a schematic illustration of a ciliary actuator element as known from the prior art.

Fig. 2 is an illustration of a prior art driving scheme where polarity of voltage is reversed per frame.

Fig. 3 illustrates a driving scheme according to a first embodiment of the present invention, as well as corresponding states of an actuator element.

Fig. 4 illustrates a driving scheme according to a second embodiment of the present invention, as well as corresponding states of an actuator element. Fig. 5 illustrates the response of an actuator element to different driving waveforms: (1) ± 60 V, (2) ± 120 V then ± 80 V, (3) ± 120 V then ± 60 V, (4) ± 120 V then ± 40 V, ± 120 V then ± 60 V (extended).

Fig. 6 illustrates roll-back for release at 40 Volts and for immediately "off". Fig. 7 illustrates a driving scheme according to a third embodiment of the present invention, with three phase driving, as well as corresponding states of an actuator element.

Fig. 8 is a schematic illustration of cross-sections of a microchannel having the inner side of its wall covered with actuator elements that curl up and straighten out when actuated, and which can be used with a driving scheme in accordance with embodiments of the present invention.

DESCRIPTION OF PREFERRED 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.

Moreover, the terms top, bottom, over, under 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.

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.

A micro-fluidic system may comprise at least one micro-channel 33 and at least one integrated micro-fluidic element, also called integrated actuator element 16, at an inner side 35 of a wall 36 of the at least one micro-channel 33 - see Fig. 8. The actuator element 16, in the example given the plurality of actuator elements 16, may be, for example, in any of the embodiments of the present invention unimorphs or bimorphs or multimorphs. According to the invention, the integrated micro-fluidic actuator elements 16 may preferably be based on polymer materials. Suitable materials 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 for the actuator elements. The materials that may be used to form actuator elements should be such that the formed actuator elements have the following characteristics: the actuator element should be compliant, i.e. not stiff, the actuator element should be tough, not brittle, the actuator elements should respond to a certain stimulus such as an electric field 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 material that is 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. Most types of polymers can be used, 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 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). A disadvantage of metals, however, could be mechanical fatigue and cost of processing.

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.

Traditional materials that show this mechanical response, and that may be applied to form actuator elements for use in the methods according to 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-aluminum-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 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, 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, the actuator elements may preferably be formed of, or include as a part of their construction, polymer materials. Therefore, in the further description, the invention will be described by means of polymer actuator elements. It has, however, to be understood by a person skilled in the art that the present invention may also be applied when other materials than polymers, as described above, are used to form the actuator elements. 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.

The polymer actuator elements may, for example, comprise an acrylate polymer, a poly(ethylene glycol) polymer comprising copolymers, or may comprise any other suitable polymer. Preferably, the polymers the polymer actuator elements are formed of should be biocompatible polymers such that they have minimal (bio)chemical interactions with the fluid in the micro-channels or the components of the fluid in the micro-channels. Alternatively, the polymer actuator elements may be modified so as to control non-specific adsorption properties and wettability. The polymer actuator elements may, for example, comprise a composite material. For example, it may comprise a particle-filled matrix material or a multilayer structure. Also "liquid crystal polymer network materials" may be used in accordance with embodiments of the present invention.

Actuator elements formed of materials which can respond to electrostatic field, electric field, may be used according to the invention. Suitable materials can be identified from the above book by Bar-Cohen. The basic idea behind artificial cilia manipulating fluids on a small scale is independent of the material the actuator means is formed of. In the description, electrical actuation will be discussed. An example of polymer material that may be used for forming actuator elements which are being electrically stimulated may be a ferroelectric polymer, i.e. polyvinylidene fluorine (PVDF). Generally, all suitable polymers with low elastic stiffness and high dielectric constant may be used to induce large actuation strain by subjecting them to an electric field. Other suitable polymers may for example be Ionomeric Polymer-Metal Composite (IPMC) materials or e.g. perfluorsulfonate and perfluorcarbonate. Examples of temperature driven polymer materials may be shape memory polymers (SMP's), which are thermally responsive polymer gels.

The present invention proposes a driving scheme for the actuation of actuator elements 16, in particular e.g. polymer MEMS, in micro-fluidic systems, in the presence of a conducting liquid such as a water based bio-liquid. The actuation may be electrical actuation. The actuation mechanism according to embodiments of the present invention may be used rather than the balanced DC driving scheme described in the prior art.

According to the present invention, the driving scheme comprises applying a force field, e.g. a voltage waveform in case of electrical actuation, at least part of the force field comprising pulses at a frequency above 50 Hz, preferably between 50 Hz and 50 kHz, more preferred between 500 Hz and 50 kHz, yet more preferred between IkHz and 5OkHz.

Hereinafter, the embodiments of the present invention are illustrated referring to electrical actuation. In case of electrical actuation, according to an embodiment of the present invention, applying such high frequency force field avoids electrolysis. Furthermore, due to the high frequency, i.e. a frequency above 50 Hz, preferably above 500 Hz, and still more preferred above 1 kHz, this also immobilizes ions and avoids that the ionic species in the fluid build up a layer of opposite charge at the electrodes, thus compensating for the externally applied field and preventing the actuator elements from moving. When the driving signals are of a sufficiently high frequency, the ions in the liquid cannot respond to the electrical field, due to the fact that the ions in the sample liquid do not have a sufficient high mobility. Therefore, they are effectively immobilized at high frequency drive signals, thus avoiding shielding of the electrical fields via charge in the fluid. Besides this, high frequency fields also avoid internal charge polarization of the insulator layer part of the actuator element 16 and subsequent surface charge and sticking of the actuator element 16. At the same time, however, the force on the actuator elements 16, which is only dependent on the amplitude and not the polarity of the applied voltage, is unaffected. The waveform in accordance with this embodiment of the present invention, as well as the corresponding state of an actuator element 16 which is rolled up in non-actuated state, is illustrated in Fig. 3. There is no upper limit to this frequency, but given that power dissipation increases with frequency it is advisable to limit the frequency to as low as possible. The lower limit of this frequency is only dependent on the type of ions in the solution and not the concentration of ions or the dimensions of the actuator elements 16.

The electrical actuation as in the first embodiment often requires voltages in excess of 100 V. It would be advantageous if these voltages could be lower. There are several negative effects of such high voltages on the actuator elements 16. These are (i) the insulating layer 13 is continually stressed and this can therefore easily result in electrical breakdown, (ii) the leakage current at high voltages can still lead to electrolysis and charging even when AC driving as in the present invention is used, i.e. with stimuli having a frequency above 50 Hz, preferably between 50 Hz and 50 kHz, more preferred between 500 Hz and 50 kHz, yet more preferred between 1 kHz and 50 kHz and (iii) the power which is dissipated can result in heating of the sample liquid and, in the case that the sample contains either proteins or cells, the biological sample can be destroyed.

According to a second embodiment of the present invention, an amended driving scheme for actuation of actuator elements 16, e.g. polymer MEMS, is provided. The driving scheme makes use of the electrical hysteresis present in actuator elements 16, e.g. polymer MEMS structures. That is, the voltage required for change of shape, e.g. roll-out, is significantly higher than that required to hold the actuator element 16 in the changed shape position, e.g. the extended position after roll-out. In other words, the state of the actuator element 16 depends on whether the voltage is approached from the low voltage or from the high voltage side. At the same time this also gives maximum flexibility for increasing the flow rate.

Therefore, rather than applying the voltage pulses as in the first embodiment and as illustrated in Fig. 3, according to the second embodiment it is advisable to first apply a series of pulses sufficient to change the shape of the actuator element 16, e.g. to roll the actuator element 16 out, e.g. electrical pulses with an amplitude of 120V and a frequency above 50 Hz, and then reduce this to a lower voltage which is sufficient to keep the actuator element 16 in the shape-changed position, e.g. in the rolled-out position. This type of driving makes direct use of the hysteresis which is present in the actuator elements 16. This method of actuation is shown schematically in Fig. 4 and offers a solution to the problems described above. It is to be noted that the number of pulses is preferably always even for both the high and low voltage pulse periods. This avoids internal charging of the insulator layer 13 part of the ciliary actuator element 16.

It is an advantage of this driving scheme according to the second embodiment that it has been optimized to reduce the power required for actuation. In order to test the second embodiment of the present invention, the motion of an actuator element 16 was filmed using a high speed camera. The actuator element 16, in this case, had a length of 100 microns, a width of 20 microns, and was made up of a 20 nm Cr layer 14 and a 1 micron polyimide layer 13. The initial radius of curvature of the actuator element 16 was 50 microns. The bottom electrode 11 was covered with a 1 micron thick siliconoxide-siliconnitride stack 12. The resulting structure was then analyzed using a lab- view routine which locates the end of the actuator element 16 in each frame and plots this as a function of time.

In Fig. 5 the state of an actuator element 16, as derived from such films, is shown for various driving waveforms. These waveforms have a frequency of 1 kHz and are split into two phases. The high voltage phase (first AC pulse) and the low voltage phase (following pulses).

In some cases the low and high voltage phases are the same voltage amplitude. This is the case in the first waveform were the voltage is set to ± 60V in both phases. As can be seen in Fig. 5 (trace 1) this is insufficient to cause change of shape, in the embodiment illustrated roll-out, and the actuator element 16 is only very slightly perturbed from its equilibrium position via the applied voltage.

Next a square wave of ±120 V was applied and this resulted in full change of shape, in the example illustrated roll-out (not shown in Fig. 5).

Then the two-phase driving according to embodiments of the present invention was applied, beginning with a high voltage phase of ±120 V and followed by a low voltage phase of either, ± 40 V, ± 60 V or ± 80 V. For the case of a low voltage phase of ± 80 V (trace 2 in Fig. 5), the actuator element 16 stays in the rolled out position in the low voltage phase and only rolls back when the voltage is switched off. This is also the case when ± 60 V is applied in the low voltage phase (trace 3). For ± 40 V being applied during the low voltage phase, the low voltage is insufficient and the actuator element 16 rolls back even before the voltage is switched off (trace 4). As a final proof of concept a high voltage phase of ±120 V was applied and the low voltage of ± 60 V was not switched off but remained on. This resulted in trace 5 in Fig. 5, and as can be seen the actuator element 16 remained in the rolled-out state for the full time that ± 60 V is applied.

In most realistic cases the period of time when the high voltage phase is applied will be much shorter than that of the low voltage phase. When considering the power consumed by the actuator elements 16 it is therefore important to reduce the voltage during the low voltage phase. In case of a low voltage phase of ± 60 V, this is 50% of the voltage that would normally be used when utilizing the driving scheme of the first embodiment. Since the power consumption is proportional to the actuation amplitude, this translates to a 50% saving in power by using the method according to the second embodiment. This is an advantage in particular for example when these actuator elements 16 are incorporated in a hand-held device where power consumption can be an issue.

Furthermore, the lower voltage reduces charging of the insulator layer 13 and also the risk of breakdown. Also, heating of the environment (e.g. fluid) of the actuator element 16 is greatly reduced. When the actuator elements 16 are to be released in the driving scheme according to the second embodiment, the voltage is simply set to zero and the internal stress of the actuator elements 16 creates the change of state back to the unactuated shape, e.g. the roll-back. The time of the change of state back to the unactuated state, e.g. roll-back time, is therefore defined by the internal stress of the actuator element 16, e.g. the polyimide- chromium film, and can only be tuned by tuning the material properties and the thickness of the layers 13, 14. From Fig. 5, it can be seen that the roll-back time is approximately 2 ms and as would be expected is independent of the voltage applied during the low voltage phase. To be able to transport fluid in a certain direction, for example from the left to the right through a micro-channel channel, the movement of the actuator elements 16 must be asymmetric. That is, the nature of a "beating" stroke should be different from that of the

"recovery" stroke. This may be achieved by a fast beating stroke and a much slower recovery stroke. As can be seen from Fig. 5, the roll-back time (recovery stroke) is approximately a factor of seven longer than that the time needed for roll-out (beating stroke; 0.3 ms). This asymmetry is the reason that these actuator elements 16 are so effective in pumping liquid. It is preferable to be able to make the times for change of shape, i.e. roll-out and roll-back time, even more asymmetric than they already are. Therefore, according to a third embodiment of the present invention, changing the timing for the change of shape is possible by not switching the voltage off when roll-back is required but by reducing it to below the voltage required to overcome the hysteresis. This could, for the examples of materials given above, be for example ± 40 V. The preferred driving scheme in accordance with the third embodiment of the present invention thus has three phases; a high voltage "select phase" 70, a lower voltage "sustain phase" 71 and a final "release phase" 72. These are shown schematically in Fig. 7. In Fig. 6 the position of an actuator element 16 is shown as a function of time where the voltage is not switched off but lowered to a voltage below the voltage required to overcome the hysteresis of the actuator element 16, e.g. to a voltage below ± 60 V, e.g. to ± 40 V (trace 61). For comparison a roll-back when the voltage is switched off is also shown (trace 60). As can be seen from Fig. 6, this way the original roll-back period of e.g. 2 ms may be extended to a longer period, e.g. 6 ms. It is advantageous that this will lead to a higher pump efficiency than that described in the second embodiment.

In order to drive the actuator elements 16 they can be grouped together in groups and driven with an active matrix such as that applied for large area electronic devices (e.g. LCD screens). While it is possible to simply incorporate a switch at the electrode structure that is to be switched, it is often beneficial to incorporate a frequency oscillator on the glass at each electrode. This avoids power dissipation in the lines that would otherwise have to carry high frequency signals.

The actuator elements 16 at the inner side 35 of the walls 36 of the micro- channels 33 may, in embodiments of the invention, be arranged in one or more rows. As an example only, the actuator elements 16 may be arranged in two rows of actuator elements 16, i.e. a first row of actuator elements 16 on a first position at the inner side 35 of the wall 36 and a second row of actuator elements 16 at a second position of the inner side 35 of the wall 36, the first and second position being substantially opposite to each other. In other embodiments of to the present invention, the actuator elements 16 may also be arranged in a plurality of rows of actuator elements which may be arranged to form, for example, a two- dimensional array. In still further embodiments, the actuator elements 16 may be randomly positioned at the inner side 35 of the wall 36 of a micro-channel 33. For an array of actuators advantage may be taken of the hysteresis effect to allow passive addressing as is familiar for display technology.

For a pumping device the motion of the actuator elements 16 is provided by a metachronic controller. This can be done by providing means for addressing the actuator elements 16 either individually or row by row. In case of, for example, electrostatic actuation this may be achieved by a patterned electrode structure that is part of a wall 36 of a microchannel 33. The patterned electrode structure may comprise a structured film, which film may be a metal or another suitable conductive film. Structuring of the film may be done by, for example, using lithography. The patterned structures can be individually addressed.

In above-described cases, individual or row-by-row stimulation of the actuator elements 16 is possible since the wall 36 of the microchannel 33 comprises a structured pattern through which the stimulus is activated. By proper addressing in time, a co-ordinated stimulation, for example, in a wave-like manner, is made possible. Non-co-ordinated or random actuator means, symplectic metachronic actuator means and antiplectic metachronic actuator means are included within the scope of the present invention. In the example shown in Fig. 8, all actuator elements 16, also those on different rows, move simultaneously. The functioning of the polymer actuator elements 16 may be improved by individual addressing of the actuator elements 16 or of the rows of actuator elements 16, so that their movement is out of phase. In, for example, electrically stimulated actuator elements 16, this may be performed by using patterned electrodes which may be integrated into the walls 36 of the micro-channel 33 (not shown in the drawing).

Thus, the motion of actuator elements 16 appears as a wave passing over the inner side 35 of the wall 36 of the micro-channel 33. The means for providing the movement may generate a wave movement that may pass in the same direction as the effective beating movement ("symplectic metachronism") or in the opposite direction ("antiplectic metachronism"). To, for example, obtain local mixing in a micro-channel 33 of a micro-fluidic system, the motion of the actuator elements 16 may be deliberately made uncorrelated, i.e. some actuator elements 16 may move in one direction whereas other actuator elements 16 may move in the opposite direction in an uncorrelated way so as to create local chaotic mixing. Vortices may be created by opposite movements of the actuator elements 16 on e.g. opposite positions of the walls 36 of the micro-channel 33.

A micro-fluidic system according to embodiments of the present invention, with an applied force field wherein at least part of the force field comprises stimuli at a frequency above 500 Hz, may be used in biotechnological 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. A micro-fluidic system in accordance with embodiments of the present invention may be used in biosensors for example, for the detection of at least one target molecule, such as proteins, antibodies, nucleic acids (e.g. DNR, RNA), peptides, oligo- or polysaccharides or sugars, in, for example, biological fluids, such as saliva, sputum, blood, blood plasma, interstitial fluid or urine. Therefore, a small sample of the fluid (e.g. a droplet) is supplied to the device, and by manipulation of the fluid within a micro-channel system, the fluid is led to the sensing position where the actual detection takes place. By using various sensors in the micro-fluidic system according to the present invention, different types of target molecules may be detected in one analysis run.

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 and spirit of this invention. For example, while the invention has been described by means of a multi-phase driving scheme for electrical actuation, the invention is not limited thereto. The driving method is considered to be a general method, which is independent of the actuation mechanism, and can also be used for e.g. optical, magnetic or thermal actuation. The method describes, in embodiments, the use of a plurality of phases, in which the applied force field is different. In combination with the mechanical properties of the actuator elements, such a multi-phase variation in force field is used to optimize the control of the actuator element while reducing the power.

Furthermore, the present invention has been illustrated by means of actuator elements 16 which, in a non-actuated state, i.e. when no external stimuli are applied to the actuator element 16, are curved. However, in accordance with other embodiments of the present invention, the actuator elements 16 may, in non-actuated stated, be straight, while they are curved in actuated state. An external stimulus, such as, for example, an electric field such as a current, electromagnetic radiation such as light, a magnetic field, a temperature change, presence of a specific chemical species, a pH change or any other suitable means, applied to the actuator elements 16, causes them to bend or straighten out or in other words, causes them to be set in motion. The change in shape of the actuator elements 16 sets the surrounding fluid, which is present in the micro-channel of the micro-fluidic system, in motion.

Claims

CLAIMS:

1. A micro -fluidic system comprising at least one micro-channel (33) having a wall (36) with an inner side (35), wherein the micro-fluidic system furthermore comprises: at least one ciliary actuator element (16) attached to said inner side (35) of said wall (36), the at least one ciliary actuator element (16) having a shape and an orientation, and - a stimulus applicator for applying a force field to said at least one ciliary actuator elements (16) so as to cause a change in its shape and/or orientation, wherein the stimulus applicator is adapted for applying a force field such that least part of the force field comprises stimuli at a frequency above 50 Hz.

2. A micro-fluidic system according to claim 1, wherein the stimuli of the at least part of the force field have a frequency between 50 Hz and 50 kHz.

3. A micro-fluidic system according to any of the previous claims, wherein the force field is a multi-phase force field, at least two of the phases having a different force field amplitude and/or force field frequency, and wherein at least one of the phases comprises stimuli at a frequency above 50 Hz.

4. A micro-fluidic system according to claim 3, wherein the force field during an earlier phase has a higher amplitude than the force field during a later phase.

5. A micro-fluidic system according to any of claims 3 or 4, wherein the force field during a first phase is sufficient to cause a change in shape and/or orientation of the ciliary actuator element (16).

6. A micro-fluidic system according to claim 5, wherein the force field during a second phase later than the first phase is sufficient to maintain the changed shape and/or orientation of the ciliary actuator element (16).

7. A micro -fluidic system according to claim 6, wherein the force field during a third phase later than the second phase has an amplitude below the electrical hysteresis voltage of the at least one actuator element (16).

8. A micro-fluidic system according to any of the previous claims, the force field being periodic, wherein the number of pulses of one period of the force field is even.

9. A micro-fluidic system according to any of claims 3 to 8, wherein the number of pulses of each phase of the force field is even.

10. A micro-fluidic system according to any of the previous claims, wherein said stimulus applicator to said at least one ciliary actuator element is an electric field generating means.

11. A micro-fluidic system according to claim 10, wherein the electric field generating means is provided by large-area electronics.

12. A method for controlling a fluid flow through a micro-channel (33) of a micro- fluidic system, the micro-channel (33) having a wall (36) with an inner side (35) provided with at least one ciliary actuator element (16), the at least one ciliary actuator element (16) having a shape and an orientation, the method comprising applying a force field to said at least one ciliary actuator element (16) so as to cause a change in its shape and/or orientation, wherein at least part of the force field comprises stimuli at a frequency above 50 Hz.

13. A method according to claim 12, wherein applying a force field comprises, during at least part of the force field, applying stimuli at a frequency between 50 Hz and 50 kHz.

14. A method according to any of claims 12 or 13, wherein applying a force field comprises applying a multi-phase force field, at least two of the phases having a different force field amplitude and/or force field frequency, wherein at least one of the phases comprises stimuli at a frequency above 50 Hz.

15. A method according to any of claims 12 to 14, wherein applying a force field to said at least one ciliary actuator element is performed by applying an electric field.

16. Use of the micro-fluidic system of any of claims 1 to 11 in biotechno logical, pharmaceutical, electrical or electronic applications.

17. A controller for controlling a fluid flow through a micro-channel (33) of a micro-fluidic system, the micro-channel (33) having a wall (36) with an inner side (35) provided with at least one ciliary actuator element (16), the at least one ciliary actuator element (16) having a shape and an orientation, the controller comprising a control unit for controlling amplitude and frequency of a force field to be applied to said at least one ciliary actuator element (16) so as to cause a change in its shape and/or orientation, the control unit being adapted to provide a force field, wherein at least part of the force field comprises stimuli at a frequency above 50 Hz.

18. A controller according to claim 17, wherein the control unit is adapted for controlling application of a multi-phase force field, at least two of the phases having a different force field amplitude and/or force field frequency, and wherein at least one of the phases comprises stimuli at a frequency above 50 Hz.

19. A controller according to claim 18, wherein the control unit is adapted to control application of a force field which during an earlier phase has a higher amplitude than during a later phase.

20. A controller according to any of claims 17 to 19, wherein the control unit is adapted to control application of a periodic force field so that the number of pulses of one period of the force field is even.

21. A controller according to any of claims 18 to 20, wherein the control unit is adapted to control application of a multi-phase force field so that the number of pulses of each phase of the force field is even.