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WO2008139401A2 - Dispositif et procédé de manipulation d'un échantillon fluidique - Google Patents

Dispositif et procédé de manipulation d'un échantillon fluidique Download PDF

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Publication number
WO2008139401A2
WO2008139401A2 PCT/IB2008/051847 IB2008051847W WO2008139401A2 WO 2008139401 A2 WO2008139401 A2 WO 2008139401A2 IB 2008051847 W IB2008051847 W IB 2008051847W WO 2008139401 A2 WO2008139401 A2 WO 2008139401A2
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WO
WIPO (PCT)
Prior art keywords
segments
fluidic
actuator units
sample
actuator
Prior art date
Application number
PCT/IB2008/051847
Other languages
English (en)
Other versions
WO2008139401A3 (fr
Inventor
Jacob M. J. Den Toonder
Original Assignee
Koninklijke Philips Electronics N.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
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Application filed by Koninklijke Philips Electronics N.V. filed Critical Koninklijke Philips Electronics N.V.
Publication of WO2008139401A2 publication Critical patent/WO2008139401A2/fr
Publication of WO2008139401A3 publication Critical patent/WO2008139401A3/fr

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
    • B01L3/50273—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip characterised by the means or forces applied to move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/30—Micromixers
    • B01F33/3038—Micromixers using ciliary stirrers to move or stir the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0887—Laminated structure
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0484—Cantilevers

Definitions

  • the invention relates to a device for handling a fluidic sample. Moreover, the invention relates to a method of handling a fluidic sample.
  • Biochips for (bio)chemical analysis 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.
  • 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, sorting and molecule detection.
  • microfluidic devices there is a basic need to control fluid flow, that is, fluids need to be transported, mixed, separated and directed through a microchannel system comprising channels with a typical width of 0.1 mm.
  • Various actuation mechanisms have been developed and are used such as pressure-driven schemes, micro-fabricated mechanical valves and pumps, inkjet-type pumps, electrokinetically controlled flows, and surface-acoustic waves.
  • the transportation of fluid and in particular of the biological particles within that fluid is crucial.
  • the biological material has to be transported to a lyzing stage and then to PCR chambers, before being taken to an analysis stage.
  • actuation methods available for the transportation of the bio- fluid. These include electrical actuation, electrophoresis and electroosmosis, capillary movement, pressure driving via MEMS, thermal gradients, etc.
  • MEMS micro-electro-mechanical systems
  • MEMS micro-electro-mechanical systems
  • Stroock et al. 2002 "Chaotic Mixer for Microchannels", Science, Vol. 295, pp. 647 to 651 disclose a solution to mix solutions in mieroenanneSs. Under typical operating conditions, flows in these channels are laminar - the spontaneous fluctuations of velocity that tend to homogenize fluids in turbulent flows are absent, and, at the same time, molecular diffusion across the channels is slow. Stroock et al. 2002 present a passive method for mixing streams of steady pressure-driven flows in microchanncls at low Reynolds number. This method uses bas-relief structures on the floor of the channel that are fabricated with commonly used methods of planar lithography. However, the mixing performance of the devices proposed by Stroock et al.
  • a device for handling a fluidic sample comprising a fluidic structure being divided in a plurality of segments, a plurality of actuator units arranged on and/or in the fluidic structure, wherein each of the plurality of segments comprises at least two of the plurality of actuator units, and an activation unit adapted to address each of the segments individually or simultaneously, to force the at least two actuator units of the addressed segment to move in a manner to mix a fluidic sample located in the fluidic structure.
  • a method of handling a fluidic sample comprising individually or simultaneously addressing each of a plurality of segments of a fluidic structure to force at least two actuator units assigned to each of the addressed segments to move in a manner to mix a fluidic sample located in the fluidic structure.
  • fluid structure may particularly denote any structure through which a fluid may be guided.
  • a fluid may be a liquid, a gas, or even a combination of these two phases. It is also possible that solid components are included in such a fluid.
  • a fluidic structure may particularly be a well, a channel or another volume through which the fluid may flow.
  • segments may particularly denote spatially delimited portions of the fluidic structure.
  • the fluidic structure is segmented or subdivided in these segments.
  • the segments may be defined as portions being individually or simultaneously addressable or controllable by an electronic control unit.
  • actuator units may particularly denote physical structures which can be moved in a controlled manner, for instance by applying electrical, magnetic, mechanical, thermally induced, or light-induced forces to the actuator units.
  • Such actuator units may be blades, flaps, or rods which can be moved within a fluidic structure to thereby provide a flow resistance for a fluid flowing through the fluidic structure.
  • the actuator units may accelerate the fluid or may force the fluid to flow in a modified direction, for instance in a reverse direction or in a direction perpendicular to a main flow.
  • activation unit may particularly denote any electric unit which can generate signals resulting in a motion of a corresponding actuator unit. Such signals may be supplied to individual segments or to individual actuator units of a segment, for instance via column lines and row lines.
  • (fluidic) sample may particularly denote any solid, liquid or gaseous substance to be analyzed, or a combination thereof.
  • the substance may be a liquid or suspension, furthermore particularly a biological substance.
  • Such a substance may comprise proteins, polypeptides, nucleic acids, lipids, carbohydrates, cells, etc.
  • a “substrate” may be made of any suitable material, like glass, plastics, or a semiconductor.
  • the term “substrate” may be thus used to define generally the elements for layers that underlie and/or overlie a layer or portions of interest.
  • the "substrate” may be any other base on which a layer is formed, for example a glass or metal layer.
  • sample chamber may particularly denote a three-dimensional volume which is provided to accommodate a sample. This volume may be, for instance, in the order of magnitude of milliliters, microliters or nanoliters.
  • the term "actuator device” may particularly denote any device having a mechanically movable/bendable/turnable component which may be employed to handle (such as to mix or to transport) a fluid (such as a liquid, particularly an aqueous sample, or a gas).
  • a fluid such as a liquid, particularly an aqueous sample, or a gas.
  • Such an actuator device may be in an inactive state, in which an actuator unit (such as an actuator beam) statically rests on a surface of a substrate or in defined relationship to a substrate.
  • an actuator unit such as an actuator beam
  • the actuator unit When the actuator unit is activated using an electrical signal applied to an electrode structure provided in the environment of the actuator unit, the actuator unit may be moved under the influence of an electric or magnetic force, or by thermally or optically induces forces.
  • micro-electro-mechanical systems may denote the technology of integrating mechanical elements, sensors, actuators, and electronics on a common substrate through microfabrication technologies.
  • Micro-electro-mechanical systems may be devices and machines fabricated using techniques generally used in microelectronics, particularly to integrate mechanical or hydraulic functions, etc. with electrical functions.
  • Micro-electro-mechanical systems may integrate mechanical structures with microelectronics. Applications include sample handling systems, medical devices, and microfluidic devices.
  • a fluidic structure is divided in several segments.
  • an efficient mixing scheme may be achieved, since adjacent segments may also be operated inversely to each other.
  • This may allow to define even complex motion schemes in which, for example, a portion of segments move their assigned actuator units in a first direction, wherein other segments move their actuator units in a second direction which may be different (for instance opposite or orthogonal) to the first direction.
  • This may allow for an intense mixture of components of the fluidic sample.
  • This may also be achieved by arranging the geometrical lay-out of the actuator units differently for different segments, and addressing the segments simultaneously.
  • the implementation of active mixing units in a fluid channel according to an exemplary embodiment of the invention may provide a significantly improved mixing performance as compared to passive solutions in which the actuators cannot be actively controlled or regulated. Therefore, particularly biological samples may be efficiently mixed, for instance to promote biological or chemical reactions or interactions between components in the fluid or to improve homogeneity of a multi-component sample. Therefore, embodiments of the invention may allow to efficiently mix even samples of a very small volume in the order of magnitude of microliters or less.
  • microchannels Mixing over short distances (for instance less than 1 cm) in microchannels is difficult.
  • active mixing in a micro- channel is made possible.
  • Specific patterns of rollable devices may be attached to the microchannel wall enabling a controlled flow perpendicular (or in another desired direction) to a horizontal main flow.
  • Advantages according to an exemplary embodiment of the invention are that a substantially enhanced mixing speed is obtainable compared to conventional purely passive micro -mixers, that the effect can be switched on or off, and that the driving of the actuators can be adjusted to the specific needs in the system (for instance depending on the viscosity of the liquid the frequency of the actuation can be changed, for instance between 1 Hz and 500 Hz).
  • a mixing channel design using polymer actuator elements is provided. Configurations are disclosed that lead to mixing.
  • a fluid is pumped through a micro-channel by external means, for example by an external pump.
  • the channel is divided in segments of a certain length, and each segment contains a pattern on the surface that causes a secondary flow. Since the pattern is different for consecutive segments, different secondary flow patterns are generated in the different segments.
  • the changing flow patterns when designed in a proper way, lead to mixing of the fluid as it travels through the channel.
  • the passive mixing grooves may be replaced by actively controllable actuator structures such as polymer actuators. The active nature of such an embodiment may lead to enhanced mixing, while the effect can also be switched off and on at will.
  • Exemplary embodiments may be implemented in microfluidic systems, biosensors, and a lab-on-chip.
  • exemplary embodiments of the invention may be applied in biotechno logical or biomedical applications such as biosensors, rapid DNA separation and sizing, cell manipulation and sorting.
  • Other fields of applications are pharmaceutical applications, in particular high-throughput combinatorial testing where local mixing is essential.
  • MicroChannel cooling systems in microelectronics applications are an other field of application of exemplary embodiments.
  • the fluidic structure may comprise at least one of the group consisting of a channel and a well.
  • a fluid may flow and can be mixed by means of an actuation of the actuator units which disturb intentionally the fluid flow characteristics of the fluidic sample flowing through the channel or well.
  • Such a superpositioned influence may force a laminar flow or may even initiate a chaotic flow.
  • the device may further comprise a substrate, wherein the fluidic structure may be formed in and/or on the substrate.
  • the device may be manufactured as a monolithically integrated device thereby allowing to manufacture the device in very small dimensions, for example to treat samples in the order of magnitude of microliters to nanoliters.
  • a substrate may be a semiconductor substrate, a glass substrate, etc. and may be treated with an etching procedure to thereby form channels.
  • the plurality of actuator units may be arranged on at least a part of a wall of the fluidic structure, particularly on a bottom wall and/or a top wall and/or a lateral wall of the fluidic structure.
  • the actuation unit may be adapted to force a first part of the actuator units to move along a first (for instance forward) direction and to force a second part of the actuator units to move along a second (for instance backward) direction, wherein the first direction may be different from the second direction, particularly may be opposite to the second direction.
  • a part of the actuator units may induce a backflow and another part of the actuator units may induce a forward flow of portions of the fluidic sample, thereby bringing particles or components of the fluidic sample in functional contact to one another.
  • the device may comprise a fluid transport unit (such as a pump, for instance a peristaltic pump, a syringe pump, or pressurized air) for transporting a fluidic sample along a flowing direction through the fluidic structure, wherein the activation unit may be adapted to force at least a part of the actuator units to move opposite to the flowing direction, or in a direction not parallel to the flowing direction of the fluidic sample, for example perpendicular to it, through the fluidic structure to thereby promote mixing of the fluidic sample.
  • the function of the fluid transport unit may be coordinated with the function of the activation unit, so that a main transport direction of the fluid may differ from a fluid flow direction forced or promoted by the activation unit.
  • a transport of the fluid may be sufficiently combined and harmonized with a selective mixing, wherein the (chaotic) mixing forces may be significantly lower than the transport forces to allow for a simultaneous mixing and transporting.
  • the segments may be arranged as an alternating sequence of first segments and second segments, wherein the activation unit may be adapted to address the first segments in common and to separately address the second segments in common.
  • the activation unit may be adapted to address the first segments in common and to separately address the second segments in common.
  • A when the first segments are denoted with A and the second segments are denoted with B, a sequence ABAB... can be generated.
  • the geometrical arrangement of the actuator units may be different in the different segments, for example in an ABAB... sequence, such that the direction or nature of the movement of the actuator units in the different segments is different, even when addressing the segments simultaneously. This may lead to a mixing effect even when the segments are addressed simultaneously.
  • the at least two actuator units assigned exclusively to one of the plurality of segments may be arranged in rows and/or columns. By such a one-dimensional or two- dimensional array of actuator units, the mixing performance may be further improved.
  • the activation unit may be adapted to address the segments depending on a present operation parameter of the device, particularly depending on a viscosity of a fluidic sample.
  • a parameter characterizing an assay or an experiment such as a viscosity of a presently investigated or treated fluidic sample, may be measured, for instance by a sensor. Based on the sensor result, the fluid flow and mixing performance may be improved or even optimized by a corresponding addressing of the segments.
  • At least a part of the plurality of actuator units may be configured as a polymeric micro-actuator. Such a polymeric micro-actuator in a configuration as an electrostatically activatible polymer composition structure is shown, for instance, in Fig. 2.
  • the micro-actuator In the non-actuated state, the micro-actuator is bending away from the substrate.
  • a configuration may include a layer structure of an electrically conductive layer and a dielectric (for instance polymer) layer, wherein the generation of an electrostatic force by applying an electrical potential difference between an electrode (which may be integrated in the substrate) and the conductive layer of the structure may force such a micro-actuator to roll out to thereby efficiently generate mixing forces.
  • the activation unit may be adapted to individually address each of the segments to force the at least two actuator units of the addressed segment to move relative to each other in a manner to mix a fluidic sample located in the fluidic structure.
  • Such a motion relative to each other may include a configuration in which adjacent actuator units approach each other in one operation state, whereas, in another operation state, both adjacent actuators are simultaneously departing from one another.
  • a first half of the duty cycle of both actuator units is characterized by an approaching of the actuator units, whereas the other half of the duty cycle, the distance between tips of the actuator units is increased.
  • the actuator device may be adapted as a microfluidic device, that is to say as a device dimensioned, designed (for instance regarding materials), capable or adapted to treat or handle microfluidic samples.
  • the actuator device may be a micro-electro-mechanical system (MEMS), for instance a micro-electro-mechanical fluid mixer.
  • MEMS micro-electro-mechanical system
  • oscillation of the actuator unit by generating alternating attracting and repulsive forces may mix the individual components.
  • the actuator device may be a sensor device (particularly a biosensor device), a biochip, a lab-on-chip, an electrophoresis device, a sample transport device, a sample mix device, a cell lyzing device, a sample washing device, a sample purification device, a sample amplification device, a polymerase chain reaction (PCR) device, a sample extraction device or a hybridization analysis device.
  • the microfluidic device may be implemented in any kind of life science or diagnostic apparatus.
  • Fig. 1 shows a mixing device according to an exemplary embodiment of the invention.
  • Fig. 2 illustrates an electrostatically actuatable polymer composite structure in a schematic view.
  • Fig. 3 shows an electrostatically actuated polymer composite structure in a practical realization.
  • Fig. 4 shows a mixing configuration according to an exemplary embodiment of the invention, wherein a view of the channel wall divided into square segments containing different actuator layouts is shown.
  • Fig. 5 shows another mixing configuration according to an exemplary embodiment of the invention, wherein a view of the channel wall divided into square segments containing different actuator layouts is shown.
  • Fig. 6 illustrates further actuator layouts for mixing according to exemplary embodiments of the invention.
  • Fig. 7 and Fig. 8 show a proof of principle device for active mixing by polymer actuators.
  • Fig. 9 and Fig. 10 illustrate a visualization experiment showing mixing, wherein Fig. 9 shows actuators switched off (no mixing), and Fig. 10 shows actuators switched on (mixing).
  • Fig. 11 is a cross-sectional view of the channel (made using OCT, optical coherence tomography) showing that a secondary flow is induced due to the actuators (that are placed in the bottom of the channel).
  • Fig. 12 shows a mixing device according to an exemplary embodiment of the invention.
  • FIG. 13 Results of particle tracking experiments: (A) Top view of the actuator layout. (B) and (C) show the estimated flow speeds as a function of switching frequency and applied voltage.
  • Fig. 14 (a) Top view of the "basic flow creating element” (BFCE), consisting of four polymer micro-actuators oriented in four different directions, that can be addressed individually; (b) Top view of an array of the “basic flow creating elements” (BFCE's).
  • BFCE basic flow creating element
  • Fig. 15 Two examples of flows created by a specific addressing of the arrays of BFCE's in a micro-fluidic device.
  • a device 100 for handling a fluidic sample 101 according to an exemplary embodiment of the invention will be explained.
  • the device 100 comprises a fluidic structure 102, configured as a channel, being spatially divided in a plurality of segments 103.
  • a fluidic structure 102 configured as a channel, being spatially divided in a plurality of segments 103.
  • four segments 103 are shown, however a larger or smaller number of segments 103 is possible.
  • Each of the segments 103 has assigned (in the present embodiment) two actuator units 104 which will be explained in more detail referring to Fig. 2.
  • the actuator units 104 are arranged on and in the fluidic structure 102, more specifically on a bottom wall of the channel 102.
  • Each of the segments 103 has assigned two actuator units 104. However, the number of actuator units 104 per segment 103 may be larger than two.
  • an activation unit 105 is provided and is realized as a monolithically integrated semiconductor circuit integrated in the silicon substrate 106 and adapted to individually address each of the segments 103 to force the two actuator units 104, respectively assigned to a selected/addressed one of the segments 103, to move in a manner to mix the fluidic sample 101 located in the fluidic structure 102.
  • the fluidic sample 101 may be a biological sample such as a mixture of different protein components, a body fluid such as blood or urine, etc.
  • the activation unit 105 may drive the actuator units 104 to generate a mixing force, as will be described below in more detail.
  • the activation unit 105 may be realized by a processing unit such as a central processing unit (CPU) or a microprocessor. Furthermore, Fig. 1 shows an input/output unit 108 which is bidirectionally coupled to the activation unit 105.
  • the input/output unit 108 is a user interface via which a human user may control operation of the device 100.
  • the input/output unit 108 may comprise an input element such as a keypad, a joystick, or a button.
  • the user interface 108 may comprise an output unit such as an LCD display.
  • the input/output unit 108 is bidirectionally coupled to the processor 105 to thereby allow a user to provide control commands to or to perceive results of a performance of the device 100.
  • the device 100 comprises the semiconductor substrate 106, for instance a semiconductor chip or wafer, but can also be manufactured from other materials such as glass or plastic.
  • the channel 102 is etched in the substrate 106, or established by other means such as powderblasting or by a construction using a patterned layer e.g. from a photopatternable material, and is therefore formed as a recess in the substrate 106.
  • the activation unit 105 is adapted to force the actuator units 104 of the first segment 103 and of the third segment 103 (counted from left to right) in a first direction 109 whereas a second segment 103 and a forth segment 103 (counted from left to right) have motion directions of their actuator units 104 which are indicated with reference numeral 110.
  • the first motion direction 109 is different from the second motion direction 110 so as to provide an efficient mixing within the channel 102.
  • the actuator units 104 are arranged linearly, that is to say as a one-dimensional row.
  • a two-dimensional matrix-like arrangement with rows and columns is possible as well.
  • the motion of the actuator units 104 is performed by applying electrical signals to electrode structures 112 assigned to each of the actuator units 104.
  • the electric signals provided by the CPU 105 to the electrodes 112 are different for the different segments 103. Therefore, the sign/polarity of the electric forces acting on the polymer composite structures 113 may vary for the different segments 103, resulting in a different motion (opposite motion) of the actuators 104 in the first and third segment 103 as compared to the second and fourth segment 103.
  • the actuator unit 104 comprises an electrode 112 integrated in the substrate 106.
  • an dielectric layer 200 is provided as a isolation structure. This can be made from any isolating material, for example poly-acrylate, poly-imide, silicon-oxide, silicon-nitride, or other materials or combinations thereof.
  • an electrically conductive structure 202 is formed as a first part of a double layer 203, and may be a thin chromium layer. Other conductive materials are also possible, such as titanium, aluminum, copper, gold, etc.
  • a further polymer layer 201 is provided as the second part of the double layer structure 203 forming an actuator beam.
  • This polymer material may be made from a wide range of materials or combinations thereof, such as elastomers like silicone rubbers or poly-urethane, (semi-crystalline) or glassy polymers, for example poly-imide, poly-acrylate, and also liquid-crystal elastomers, or liquid-crystal networks.
  • elastomers like silicone rubbers or poly-urethane, (semi-crystalline) or glassy polymers, for example poly-imide, poly-acrylate, and also liquid-crystal elastomers, or liquid-crystal networks.
  • an electric signal is applied to the electrode 112 that the actuator beam 203 formed by the components 201, 202 is rolled up. It is also possible to roll down the double layer 201, 202 so that an essentially planar structure is obtained.
  • An example of an electrostatically polymer actuator 300 that can be used in this application is shown in Fig. 3.
  • Fig. 3 is a practical realization of the concept of Fig. 2
  • the actuator 104 is formed by a double-layer composite structure 203 consisting of a polymer film 201 and a conductive film 202.
  • a voltage difference is applied between the electrode 112 underneath the actuator beam 203 and the conductive film 202 that is part of the actuating structure 203, an electrostatic force will pull the structure 203 towards the substrate 106. Consequently, the structure 203 will roll out and flatten out on the substrate 106.
  • the slab will return to its original curled shape by elastic recovery.
  • a mixing flow in a micro-channel 102 may be obtained by placing the actuators 104 in the channel 102 according to a specific geometrical configuration. According to exemplary embodiments of the invention, solutions are provided how to design this arrangement to get good mixing.
  • the channel 102 may be divided into various segments 103 along its length.
  • the size of the segments 103 is naturally of the order of magnitude of the channel width, which can be from about 10 microns (or less) to about a millimeter (or more).
  • 103 contains multiple polymer actuators 104, such as the one in Fig. 2 and Fig. 3, arranged in such a way that, when actuated, a specific flow pattern is generated in the segment. This is a secondary flow superposed on the main flow that is driven, for example, by an external pump.
  • the actuator configuration in consecutive segments 103 is different, typically in an A-B-A-B-... sequence (or in an A-B-C-A-B-C-... sequence), so that different secondary flows are generated in different segments 103.
  • the sequence of different flow patterns will lead to mixing of the fluid 101 as it is pumped through the channel 102. More specific, an example of an arrangement 400 of polymer actuators 104 is shown in Fig. 4.
  • Fig. 4 depicts segments 401, 402 in an A-B-A manner, containing rows of electrostatic polymer actuators 104, viewed from the top (the actuators 104 are curled upwards in Fig. 4 and are visible as small rectangles).
  • the segments 401, 402 are present on the bottom of a micro-channel 102 with a width equal to the segment size, through which a fluid is pumped causing a main flow.
  • the polymer actuators 104 When actuated, the polymer actuators 104 will all roll out in one direction, perpendicular to the main flow, in segment A 401, and in the opposite direction in segment B 402. This will cause opposite secondary (or transverse) flows to be generated that will lead to mixing.
  • Fig. 4 is just one specific example of an arrangement 400 of polymer actuators
  • FIG. 5 Another embodiment 500 is shown in Fig. 5.
  • each of segments 501, 502 contain rows of actuators 104 with mixed roll-out directions.
  • segment 501 C three of five rows are rolling out in a specific direction perpendicular to the main flow, and the other two are rolling out in the other direction.
  • segment 502 D the asymmetry in rolling out direction is reversed. Therefore, in each segment 501, 502 two secondary, asymmetric flow patterns are generated of which the asymmetry plane is shifting between segments 501, 502. Many other arrangements are possible.
  • a common characteristic of embodiments of the invention is: consecutive segments with different arrangements, leading to different secondary flow patterns (having at least a velocity component perpendicular to the main flow).
  • Fig. 6 shows several other possible layouts 600.
  • the actuators can be placed on any wall of the channel (bottom-top- sides), or combinations of walls. Each segment may be addressed individually.
  • a proof-of-principle device 800 for active mixing by polymer actuators is shown in Fig. 7 and Fig. 8.
  • a Y-shaped mixing channel 700 has been designed and fabricated.
  • the actuators are manufactured on a glass plate.
  • the two inlets are connected to syringe pumps.
  • PDMS polydimethylsiloxane
  • the bottom channel wall is covered with actuator arrangements in sixteen segments of 1 by 1 mm, containing various actuator lay-outs, typically in an A-B-A-B-... sequence.
  • the layout shown in Fig. 4 has been used. Each individual segment can be individually addressed.
  • the main flow is driven by the syringe pumps, the movement of the actuators induces a transverse flow.
  • OCT optical coherence tomography
  • Fig. 11 is a cross-sectional view of the channel (made using OCT, optical coherence tomography) showing that a secondary flow is induced due to the actuators (that are placed in the bottom of the channel).
  • active mixing may be obtained in a micro-channel.
  • Fig. 12 shows a mixing device 1200 according to an exemplary embodiment of the invention.
  • Fig. 12 is similar to the embodiment of Fig. 1. However, the orientation of the polymer actuators 113 is oriented oppositely in consecutive segments 103. Thus, the actuator units 104 may be oriented in different directions for different segments 103, as shown in Fig. 12, so that they move in different directions when actuated (even simultaneously with the same (electrical) signal). The induced fluid flows are also oriented differently, which may lead to efficient mixing within the channel 102. According to exemplary embodiments of the invention, one electrode 112 may be shared by more than one, or even all moving structures 113. This is, effectively, what happened in the mixing experiments shown in Fig. 9 to Fig. 11.
  • the electrostatic actuators shown in Fig. 2 and Fig. 3 can induce significant fluid velocities.
  • the induced flow velocities were estimated by carrying out particle tracking experiments in silicone oil.
  • the actuators were arranged on a substrate in square segments of 1 mm 2 , as shown in a top view in Fig. 13 A.
  • the segment contains five columns of twenty actuators, visible in Fig. 13A as black rectangles since they are in the curled state.
  • the surface was covered with a 0.5 mm thick silicone oil film (viscosity 9.3 mPa s), so that the actuators were completely immersed.
  • To visualize the flow two kinds of particles were dispersed in the fluid, namely titaniumdioxide (TiO 2 ) particles with a mean diameter of 0.5 micron and hollow glass spheres with an average diameter of 12 micron.
  • the actuators were actuated with different switching frequencies and actuation voltages, and the movement of the tracer particles was recorded at 30 frames per second. Particle tracking was done manually from the obtained movies, and the induced flow velocities were estimated.
  • Fig. 13 (B) shows the induced velocity as a function of switching frequency, estimated from tracking of TiO 2 particles (solid lines) and hollow glass spheres (broken lines).
  • the applied AC voltage was 75V/lkHz.
  • Fig. 13 (C) shows the effect of applied AC voltage (always 1 kHz) on the induced velocity, measured using hollow glass spheres.
  • the switching frequency was here fixed at 50 Hz.
  • the lines are drawn as a guide to the eye.
  • Fig. 14 shows an advantageous embodiment.
  • the "basic flow-creating element" (BFCE) is shown in 14 (a). It consists of four micro-actuators, acting in four different directions. These can be the electrostatically actuated polymer MEMS, shown in Fig. 2 and Fig. 3, of which the rolling-out direction, and hence the induced direction of flow, is indicated by the arrows in Fig. 14 (a).
  • the actuator "R” will roll out to the right, and hence it will create a fluid velocity to the right (of which the magnitude depends on the applied voltage and frequency, as illustrated in Fig.
  • the under-electrode of the BFCE is divided into four segments that can be addressed individually, so that any of the polymer actuators can be driven separately.
  • arrays of many BFCE's are combined, as shown schematically in Fig. 14 (b). This structure can be integrated in a channel or in a micro-chamber of a micro-fluidic device.
  • Fig. 14(b) offers the possibility of versatile flow creation in micro-fluidic devices.
  • Fig. 15 shows two examples of flows created by a specific addressing of the arrays of BFCE's.
  • Fig. 15 (a) all segments "R" of the BFCE's are addressed, while the other segments are inactive. In each BFCE, a flow to the right is therefore induced, and thus in the whole flow system a uniform flow to the right occurs.
  • Figure 15 (b) shows an example in which a global eddy or vortex is induced by a particular driving scheme.
  • flow patterns can be created depending on the addressing scheme.
  • the flow speed can be controlled by varying the applied voltage and switching frequency. This makes this concept extremely versatile.
  • BFCE shown in Fig. 14 (a) is just one example; other BFCE's (for instance with only 3 independent directions of roll-out, or with different particular orientations), can be applied.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)

Abstract

La présente invention concerne un dispositif (100) de manipulation d'un échantillon fluidique (101), le dispositif (100) comprenant une structure fluidique (102) divisée en une pluralité de segments (103), une pluralité d'unités d'actionnement (104) agencées sur et/ou dans la structure fluidique (102), chacun parmi la pluralité de segments (103) comprenant au moins deux de la pluralité d'unités d'actionnement (104), et une unité d'activation (105) conçue pour adresser chacun des segments (103) individuellement ou simultanément pour forcer les deux unités d'actionnement ou plus (104) du segment (103) à se déplacer d'une manière à mélanger un échantillon fluidique (101) positionné dans la structure fluidique (102).
PCT/IB2008/051847 2007-05-11 2008-05-09 Dispositif et procédé de manipulation d'un échantillon fluidique WO2008139401A2 (fr)

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Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8152305B2 (en) 2004-07-16 2012-04-10 The University Of North Carolina At Chapel Hill Methods, systems, and computer program products for full spectrum projection
US8490469B2 (en) 2007-02-22 2013-07-23 The University Of North Carolina Methods and systems for multiforce high throughput screening
US8586368B2 (en) 2009-06-25 2013-11-19 The University Of North Carolina At Chapel Hill Methods and systems for using actuated surface-attached posts for assessing biofluid rheology
JP2015529557A (ja) * 2012-09-24 2015-10-08 ヒューレット−パッカード デベロップメント カンパニー エル．ピー．Ｈｅｗｌｅｔｔ‐Ｐａｃｋａｒｄ Ｄｅｖｅｌｏｐｍｅｎｔ Ｃｏｍｐａｎｙ， Ｌ．Ｐ． マイクロ流体混合装置
US9952149B2 (en) 2012-11-30 2018-04-24 The University Of North Carolina At Chapel Hill Methods, systems, and computer readable media for determining physical properties of a specimen in a portable point of care diagnostic device

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH10141300A (ja) * 1996-11-06 1998-05-26 Honda Motor Co Ltd 流体輸送装置
US6485273B1 (en) * 2000-09-01 2002-11-26 Mcnc Distributed MEMS electrostatic pumping devices
RU2381382C2 (ru) * 2005-02-21 2010-02-10 Конинклейке Филипс Электроникс Н.В. Микрофлюидальная система (варианты), способ ее изготовления и способ управления потоком текучей среды

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8152305B2 (en) 2004-07-16 2012-04-10 The University Of North Carolina At Chapel Hill Methods, systems, and computer program products for full spectrum projection
US8490469B2 (en) 2007-02-22 2013-07-23 The University Of North Carolina Methods and systems for multiforce high throughput screening
US8586368B2 (en) 2009-06-25 2013-11-19 The University Of North Carolina At Chapel Hill Methods and systems for using actuated surface-attached posts for assessing biofluid rheology
US9238869B2 (en) 2009-06-25 2016-01-19 The University Of North Carolina At Chapel Hill Methods and systems for using actuated surface-attached posts for assessing biofluid rheology
US9612185B2 (en) 2009-06-25 2017-04-04 The University Of North Carolina At Chapel Hill Methods and systems for using actuated surface-attached posts for assessing biofluid rheology
JP2015529557A (ja) * 2012-09-24 2015-10-08 ヒューレット−パッカード デベロップメント カンパニー エル．ピー．Ｈｅｗｌｅｔｔ‐Ｐａｃｋａｒｄ Ｄｅｖｅｌｏｐｍｅｎｔ Ｃｏｍｐａｎｙ， Ｌ．Ｐ． マイクロ流体混合装置
EP2850438A4 (fr) * 2012-09-24 2016-02-17 Hewlett Packard Development Co Dispositif de mélange microfluidique
US10286366B2 (en) 2012-09-24 2019-05-14 Hewlett-Packard Development Company, L.P. Microfluidic mixing device
US9952149B2 (en) 2012-11-30 2018-04-24 The University Of North Carolina At Chapel Hill Methods, systems, and computer readable media for determining physical properties of a specimen in a portable point of care diagnostic device

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