WO2008125927A2 - Système microfluidique avec actionneurs - Google Patents

Système microfluidique avec actionneurs Download PDF

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Publication number
WO2008125927A2
WO2008125927A2 PCT/IB2007/055104 IB2007055104W WO2008125927A2 WO 2008125927 A2 WO2008125927 A2 WO 2008125927A2 IB 2007055104 W IB2007055104 W IB 2007055104W WO 2008125927 A2 WO2008125927 A2 WO 2008125927A2
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WO
WIPO (PCT)
Prior art keywords
actuator
micro fluidic
sample
fluidic system
sample chamber
Prior art date
Application number
PCT/IB2007/055104
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English (en)
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WO2008125927A3 (fr
Inventor
Murray F. Gillies
Jacob M. J. Den Toonder
Marc W. G. Ponjee
Mark T. Johnson
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Koninklijke Philips Electronics N.V.
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Application filed by Koninklijke Philips Electronics N.V. filed Critical Koninklijke Philips Electronics N.V.
Publication of WO2008125927A2 publication Critical patent/WO2008125927A2/fr
Publication of WO2008125927A3 publication Critical patent/WO2008125927A3/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
    • 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
    • B01L3/502769—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 multiphase flow arrangements
    • B01L3/502784—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics
    • B01L3/502792—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 multiphase flow arrangements specially adapted for droplet or plug flow, e.g. digital microfluidics for moving individual droplets on a plate, e.g. by locally altering surface tension
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/52—Heating or cooling apparatus; Heat insulating devices with provision for submitting samples to a predetermined sequence of different temperatures, e.g. for treating nucleic acid samples
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L7/00—Heating or cooling apparatus; Heat insulating devices
    • B01L7/54—Heating or cooling apparatus; Heat insulating devices using spatial temperature gradients
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006—Micropumps
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04B—POSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00—Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/20—Other positive-displacement pumps
    • F04B19/24—Pumping by heat expansion of pumped fluid
    • F—MECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04—POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04D—NON-POSITIVE-DISPLACEMENT PUMPS
    • F04D33/00—Non-positive-displacement pumps with other than pure rotation, e.g. of oscillating type
    • 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
    • B01L2300/0819—Microarrays; Biochips
    • 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
    • B01L2300/089—Virtual walls for guiding liquids
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1822—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using Peltier elements
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1805—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks
    • B01L2300/1827—Conductive heating, heat from thermostatted solids is conducted to receptacles, e.g. heating plates, blocks using resistive heater
    • 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
    • B01L2300/18—Means for temperature control
    • B01L2300/1861—Means for temperature control using radiation
    • B01L2300/1872—Infrared light
    • 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
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0633—Valves, specific forms thereof with moving parts
    • 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
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0688—Valves, specific forms thereof surface tension valves, capillary stop, capillary break

Definitions

  • the invention relates to a micro fluidic system for manipulating a sample comprising at least one actuator, the use of such a device, and to a method for manipulating a sample.
  • a microfluidic device for the investigation of fluids which comprises actuators serving as pumps or valves that are controlled by heating elements.
  • the actuators comprise a wax plug that can be molten and then be moved by expanding gas bubbles. Said actuators are rather complicated and need several heating elements for melting and moving the wax plug.
  • microfluidic system according to claim 1, a method according to claim 18, and a use according to claim 19. Preferred embodiments are disposed in the dependent claims.
  • the microfluidic system according to the present invention is intended for the manipulation of a sample, particularly a liquid or gaseous chemical substance like a biological body fluid which may contain particles.
  • the term "manipulation" shall denote any interaction with said sample, for example measuring characteristic quantities of the sample, investigating its properties, transporting it, processing it mechanically or chemically or the like.
  • the microfluidic system comprises the following components, of which at least some belong to a microfluidic device:
  • a sample chamber in which the sample to be manipulated can be provided.
  • the sample chamber is typically an empty cavity or a cavity filled with some substance like a gel that may absorb a sample substance; it may be an open cavity, a closed cavity, or a cavity connected to other cavities by fluid connection channels.
  • the sample chamber is typically a part of a microfluidic device.
  • a heating device that is adapted to establish a predetermined spatial and/or temporal temperature profile in the sample chamber.
  • the heating device may be integrated into a microfluidic device or be an external device with respect to the microfluidic device.
  • At least one heat-sensitive actuator that is disposed in said sample chamber and that can controlledly change its spatial configuration upon a temperature change under predetermined operating conditions.
  • the "change of a configuration" shall imply a transition between two different shapes that are not simply related to each other by a scaling of their sizes; such a configuration change is therefore different from the usual expansion or shrinking that all homogeneous materials experience if temperature changes.
  • the actuator changes its configuration only if predetermined operating conditions prevail, for example a certain transition temperature, wherein said operating conditions may of course also comprise a continuous interval of values.
  • the actuator is typically a solid, structured object composed of different materials. Particular examples of actuators will be described in connection with preferred embodiments of the invention.
  • the temperature change may for example be effected by heating, cooling or illuminating the actuator.
  • the described microfluidic system has the advantage that a simple change of temperature suffices to control the actuator, wherein said temperature change can be achieved with the help of the heating device that is typically already present for other purposes.
  • the configuration change of the actuator can be used for many different purposes, e.g. for moving objects (cells, particles etc.) or fluid in the sample chamber.
  • the actuator is designed such that it can move a surrounding sample fluid and/or block or free a fluid channel.
  • the actuator can thus serve as a pump or a valve in the microfluidic system.
  • the actuator has the form of a strip that can be changed between a rolled up and an extended spatial configuration.
  • Such an actuator can be produced comparatively easily, for example by generating layered structures with methods known from microelectronics.
  • the actuator comprises liquid crystals that crystallize or melt, respectively, under the influence of heat, light, electrical fields etc.
  • liquid crystals and particular materials that can be applied in connection with the present invention can be found in the literature (for example: Dirk J. Broer, Henk van Houten, Martin Ouwerkerk, Jaap M.J. den Toonder, Paul van der Sluis, Stephen I. Klink, Rifat A.M.
  • the liquid crystals are preferably incorporated in an elastomer network, e.g. in polysiloxane. Changes of size or shape of the liquid crystals can then induce corresponding movements of the elastomer, for example in a way similar to the action of muscles at the joints of an arm.
  • the liquid crystals mentioned above preferably contain molecules that undergo isomerization under the influence of light and/or heat, wherein said molecules may particularly comprise azo-benzene groups.
  • the actuator is a heterogeneous system and comprises materials with a different thermal expansion coefficient, such that upon temperature increase of the actuator the shape of the actuator configuration changes. The temperature increase may be due to applying heat from an external source to the actuator or by internal heat generation in the actuator (e.g. infrared radiation absorption).
  • the microfluidic system may in principle comprise just one single actuator of the kind described above, it is preferred that it comprises a plurality of such actuators that are arranged in an "actuator array".
  • array shall in the context of the present invention denote an arbitrary three-dimensional arrangement of a plurality of elements (e.g. actuators). Typically such an array is two- dimensional and preferably also planar, and the elements are arranged in a regular pattern, for example a grid or matrix pattern.
  • the actuators may optionally have different characteristics of the transition of their configuration, for example different transition temperatures at which they change their spatial configuration.
  • Such a spread of transition characteristics has the advantage that, if the sample chamber is uniformly heated, the actuators do not all change their configuration simultaneously. In this way there are always some actuators during e.g. the heating of a sample chamber that change their configuration and thus guarantee a continuous mixing of the sample.
  • the actuators with different transition characteristics are distributed in a regular or in a random pattern across the actuator array to provide a spatially uniform and/or coordinated effect.
  • the at least one heat-sensitive actuator preferably changes its configuration at a transition temperature that is passed during a (physical, chemical or biochemical) reaction taking place in the sample chamber, particularly during a temperature controlled DNA amplification process such as polymerase chain reaction (PCR).
  • PCR polymerase chain reaction
  • a heating element is disposed adjacent to the at least one heat-sensitive actuator, wherein said heating element is by definition able to exchange heat with the actuator, i.e. to heat or to cool it.
  • configuration changes of the actuator can then be induced as desired.
  • Such a control of the actuator may be the only purpose of the heating element.
  • the heating element has, however, the additional (or even primary) function of exchanging heat with a sample in the sample chamber, and it may be a component of the heating device mentioned above.
  • the micro fluidic system may particularly comprise a plurality of such heating elements which are arranged in a heating array. If the micro fluidic system further comprises an actuator array, the heating elements and the actuators are preferably aligned with respect to each other. Each actuator may for example have one heating element in its vicinity.
  • said heating element is preferably adapted to operate in a pulsed mode.
  • the resulting pulsation of the heat exchange with the associated actuator allows to effect repeated configuration changes of the actuator.
  • the pulsed operation of the heating element is designed such that the pulses average out in the sample chamber. In this case, a constant temperature can be maintained in the sample chamber while the actuator in the immediate vicinity of the heating element experiences temperature fluctuations.
  • the micro fluidic system comprises a plurality of actuators and associated heating elements
  • said heating elements are preferably adapted to generate a temporal and/or spatial coordination of the actuators.
  • the heating elements may for example be activated such that a spatial wave of activation sweeps across the array of actuators. If the heating elements are operated in the aforementioned pulsed mode, the pulses in neighboring heating elements may be shifted with respect to each other to assist the averaging of temperatures in the sample chamber.
  • the micro fluidic system comprises a plurality of heating elements that have different heating characteristics.
  • the heating elements may in particular have differently tight thermal couplings to associated actuators and/or to the sample chamber. Even if all these heating elements are driven identically, e.g. with the same current, or even if the sample chamber is homogeneously heated, the resulting temperature increases in the associated actuators will be different. This guarantees that the activation of actuators (with identical transition temperatures) is spread in time during a heating process.
  • the heating elements may particularly comprise a resistive strip, a transparent electrode, a Peltier element, a radio frequency heating electrode, or a radiative heating (IR) element. All these elements can convert electrical energy into heat, wherein the Peltier element can additionally absorb heat and thus provide a cooling function.
  • the micro fluidic device comprises at least one light emitter, for example a Light Emitting Diode (LED) that is disposed adjacent to the actuator.
  • a selective control of the light emitter can be used to induce configuration changes of the associated actuator.
  • the invention further relates to a method for the manipulation of a sample in a sample chamber, wherein the temperature inside the sample chamber is controlled and wherein the spatial configuration of a heat-sensitive actuator is changed by changing its temperature (e.g. by heating, cooling, or illuminating said actuator).
  • the method comprises in general from the steps that can be executed with a microfluidic system of the kind described above. Therefore, reference is made to the preceding description for more information on the details, advantages and improvements of that method.
  • the invention further relates to the use of the microfluidic systems described above for molecular diagnostics, biological sample analysis, chemical sample analysis, food analysis, and/or forensic analysis.
  • Molecular diagnostics may for example be accomplished with the help of magnetic beads that are directly or indirectly attached to target molecules.
  • Fig. 1 schematically shows a planar view (left) and a cross section (right) of a microfluidic system according to the present invention
  • Fig. 2 schematically shows an actuator and an associated heating element of the microfluidic system of Fig. 1;
  • Fig. 3 shows a typical temperature variation as a function of time for a PCR;
  • Fig. 4 shows a DC current supply (top) and a pulsed current supply (bottom) to the heating element of Fig. 2;
  • Figs. 5 and 6 show a cross section and a planar view, respectively, of an actuator that is used to induce pressure waves at a hydrophilic or hydrophobic stop.
  • Like reference numbers in the Figures refer to identical or similar components.
  • Biochips for (bio)chemical analysis will become an important tool for a variety of medical, forensic and food applications.
  • biochips comprise a biosensor in most of which target molecules (e.g. proteins, DNA) are immobilized on biochemical surfaces with capturing molecules and subsequently detected using for instance optical, magnetic or electrical detection schemes.
  • target molecules e.g. proteins, DNA
  • magnetic biochips are described in the WO 2003/054566, WO 2003/054523, WO 2005/010542 A2, WO 2005/010543 Al, and WO 2005/038911 Al, which are incorporated into the present application by reference.
  • PCR polymerase chain reaction
  • thermocycling consists of three steps: melting of the double stranded DNA (denaturisation) to separate complementary strands, binding of the specific primers to the target site (annealing), and extension of the primers by a thermostable enzyme such as Taq polymerase (extension).
  • Typical temperatures for the denaturisation, annealing and extension steps are 94°, 40-72°, and 72°C, respectively.
  • Temperature control is used during a hybridization assay to regulate stringency of the binding of a target biomolecule to a functionalized surface, e.g. the binding of a DNA strand to its complementary strand.
  • a high stringency, and therefore accurate temperature control is required when for instance single point mutations are of interest.
  • thermocontrol on a biochip is needed in general. For example because many bio molecules are stable in a small temperature window (usually around 37°C), or become de-activated when temperatures are outside of this temperature window.
  • Fig. 1 shows in this respect an exemplary embodiment of a microfluidic system 100 that can be used for the examination of a (e.g. biological) sample in a sample chamber 1.
  • the device 100 comprises an array of individually addressable heating elements 20, e.g. resistive strips, that are realized in the shown example on the upper side of the sample chamber 1 in a substrate 51.
  • a further substrate 52 is arranged on the bottom side of the sample chamber 1 in which an array of sensor elements 53 is realized.
  • sensor elements 53 it is for example possible to detect target particles 2 (e.g. labeled biological molecules) in a sample filling the sample chamber 1.
  • the invention is not limited to any particular type of biosensor, it can be advantageously applied to biosensors based upon optical (e.g. fluorescence), magnetic or electrical (e.g. capacitive, inductive...) sensing principles.
  • the heating array with its heating elements 20 can be used to either maintain a constant temperature across the entire sensor area, or alternatively to create a defined temporal temperature profile. It may optionally comprise additional elements such as temperature sensors to enable a closed-loop control of temperature. It should be noted, however, that the invention is not limited to sensor devices with such a heating array, and that any other kind of heating device could be used to achieve desired temperatures and temperature gradients in the sample chamber.
  • Fig. 1 further shows a plurality of actuators 10 that are distributed in an actuator array across the top surface of the sample chamber 1, wherein said actuator array is in this case more sparsely occupied than the heating array.
  • each actuator 10 is disposed in the immediate vicinity of an associated heating element 20, particularly between the heating element 20 and the sample chamber 1.
  • the actuators 10 are designed such that they can be activated by heat emitted by the associated heating element 20.
  • Fig. 2 shows in this respect a more detailed, schematic cross section through an actuator 10 and the associated heating element 20.
  • the heating element 20 is for example realized by a resistance 21 coupled to a driving and control unit 22 that selectively provides a driving current I.
  • the actuator 10 consists of a film or strip 11 that is typically between 15 and 100 ⁇ m in length and made from a temperature-responsive actuating material.
  • LC liquid crystal
  • a configuration system can for example be made which upon heating through a specific temperature (the nematic isotropic temperature) undergoes a transition in the backbone of the elastomer molecules and changes length.
  • a careful control of processing conditions allows to obtain a gradient in orientation of LC molecules over the thickness of the film so that one side of the film contracts while the other expands (G.N. MoI, K.D. Harris, G.W.M. Bastiaansen, D.J.
  • Fig. 2 shows a rolled up configuration in bold and an extended configuration in dotted lines.
  • the frequency at which the actuator can be thermally actuated depends on the heater characteristics, the thermal coupling between actuator and heater, the thermal capacity of the heater, the thermal response of the actuator, the cooling rate of heater and actuator, etc.
  • the actuator 10 may also comprise materials that can be heated by the absorption of light.
  • LC-elastomer (LCE) type structures can be used to produce either mixing of a fluid as it is heated for other purposes or to produce a fluid flow via heating arrays placed under heat activated structures. Particular examples of such applications will be described in more detail in the following.
  • a first application relates to a chamber 1 with homogenous heater geometry as the one shown in Fig. 1, which can be used for DNA amplification, e.g. using PCR.
  • a typical PCR temperature cycle as it will be applied for PCR of small volumes, can be found in Fig. 3. It comprises a period during which the sample is held at 72°C, wherein the length of this period is dependent on the type of enzyme used for multiplication and the size of the DNA to be replicated. In some protocols this period may not even be necessary.
  • Fig. 4 shows the DC current supply to the heaters 20 for the first embodiment (upper diagram) and the pulsed current supply for the aforementioned second embodiment (lower diagram; current I in arbitrary units).
  • Parameters of the pulse characteristics that may be used to control the heating comprise the frequency, the offset, the pulse-height, the pulse-width, etc.
  • a single parameter or a combination of parameters may be used to create a waveform to drive the heating element.
  • waveforms of different heating elements may be related to one another, e.g. be in-phase or out-of-phase. This provides options to average out the pulse effect in the fluid (e.g. by pulsing out-of-phase actuators that are positioned close to one another), or to create specific manipulation (e.g. flow) patterns (e.g. line-by-line pulsing).
  • a microfluidic system can be created with a variety of functionalities, for example heater arrays for thermal processing, micro-fluidic structures and particle manipulation electrodes/electronics. If, for example, thermal processing is integrated on a lab-on-a-chip platform then there is no extra cost in creating subsequent heaters on other areas of the glass substrate; this facilitates the suggested use of heat-sensitive actuators on top of a heater (which is only present to actuate the actuator) to allow pumping of a fluid.
  • an actuator structure 10 could be used to generate a pressure- wave to overcome a hydrophobic or hydrophilic stop in a micro fluidic channel. This is illustrated in a cross-sectional view in Fig.
  • Heaters 20 cause a rolling or unrolling of the actuator structure 11, which in turn moves a droplet of sample fluid 2 through the channel.
  • the use of heat-sensitive actuators avoids the problems of electrolysis of the water based biological fluids that occur if direct electrical actuation is used.
  • the invention is not limited to the described applications, e.g. PCR.
  • the invention can advantageously be used in general for DNA amplification and other (bio-)chemical processes, such as DNA hybridization or bonding of proteins to anti-bodies, or DNA extraction.
  • thermally actuated device to pump or mix biological fluids in a lab-on-a-chip environment (i.e. molecular diagnostic device).
  • fluid actuators can be equipped with a heater modality specifically designed to actuate the device or can use the already existing heat sources used for instance for DNA amplification (e.g. PCR), temperature control of the biosensor and other thermal reactions on the chip.
  • the thermally actuated mixing structures can advantageously respond to an already necessary temperature variation in a sample.
  • An alternative is to use heat-sensitive actuators that experience a temperature change by absorption of electromagnetic radiation (e.g. infrared radiation).

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Clinical Laboratory Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Mechanical Engineering (AREA)
  • General Engineering & Computer Science (AREA)
  • Dispersion Chemistry (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)

Abstract

L'invention concerne un système microfluidique (100), en particulier un biocapteur, destiné à manipuler un échantillon dans une chambre d'échantillons (1). Le dispositif comprend au moins un actionneur (10) qui modifie de manière réversible sa configuration spatiale s'il est chauffé et/ou refroidi. L'actionneur (10) peut en particulier être agencé de manière adjacente à un élément de chauffage associé (20) d'un système de chauffage qui est utilisé pour établir un profil de température spatial et/ou temporel prédéterminé dans la chambre d'échantillons (1). Le changement de configuration de l'actionneur (10) peut être utilisé pour déplacer l'échantillon de fluide afin de contrôler son passage à travers des canaux de fluide. Il est possible d'agencer de manière facultative une pluralité d'actionneurs (10) qui subissent leurs changements de configuration à différentes températures, en particulier des températures comprises dans une plage qui est traversée au cours d'une réaction comme la PCR.
PCT/IB2007/055104 2006-12-19 2007-12-14 Système microfluidique avec actionneurs WO2008125927A2 (fr)

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EP06126460 2006-12-19
EP06126460.2 2006-12-19

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WO2008125927A2 true WO2008125927A2 (fr) 2008-10-23
WO2008125927A3 WO2008125927A3 (fr) 2009-01-29

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WO2019103730A1 (fr) * 2017-11-22 2019-05-31 Hewlett-Packard Development Company, L.P. Dispositifs microfluidiques de régulation de température

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US20060069425A1 (en) * 2004-09-24 2006-03-30 Searete Llc, A Limited Liability Corporation Of The Stste Of Delaware Ciliated stent-like-system
WO2006087655A1 (fr) * 2005-02-21 2006-08-24 Koninklijke Philips Electronics N.V. Systemes microfluidiques a elements de commande

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US20030156991A1 (en) * 2001-10-23 2003-08-21 William Marsh Rice University Optomechanically-responsive materials for use as light-activated actuators and valves
US20060069425A1 (en) * 2004-09-24 2006-03-30 Searete Llc, A Limited Liability Corporation Of The Stste Of Delaware Ciliated stent-like-system
WO2006087655A1 (fr) * 2005-02-21 2006-08-24 Koninklijke Philips Electronics N.V. Systemes microfluidiques a elements de commande

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2019103730A1 (fr) * 2017-11-22 2019-05-31 Hewlett-Packard Development Company, L.P. Dispositifs microfluidiques de régulation de température
US11278894B2 (en) 2017-11-22 2022-03-22 Hewlett-Packard Development Company, L.P. Temperature-controlling microfluidic devices

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