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WO2005069964A2 - Appareil et procede de deplacement de micro-gouttelettes au moyen de gradients thermiques induits par laser - Google Patents

Appareil et procede de deplacement de micro-gouttelettes au moyen de gradients thermiques induits par laser Download PDF

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Publication number
WO2005069964A2
WO2005069964A2 PCT/US2005/002033 US2005002033W WO2005069964A2 WO 2005069964 A2 WO2005069964 A2 WO 2005069964A2 US 2005002033 W US2005002033 W US 2005002033W WO 2005069964 A2 WO2005069964 A2 WO 2005069964A2
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WO
WIPO (PCT)
Prior art keywords
droplet
liquid phase
droplets
immiscible
immiscible liquid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/US2005/002033
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English (en)
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WO2005069964A3 (fr
Inventor
Gregory Faris
Kenneth T. Kotz
Kyle Noble
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SRI International Inc
Original Assignee
SRI International Inc
Stanford Research Institute
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Priority to US10/597,372 priority Critical patent/US7582858B2/en
Publication of WO2005069964A2 publication Critical patent/WO2005069964A2/fr
Publication of WO2005069964A3 publication Critical patent/WO2005069964A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • B01L3/502769—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
    • B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
    • B01F33/00—Other mixers; Mixing plants; Combinations of mixers
    • B01F33/05—Mixers using radiation, e.g. magnetic fields or microwaves to mix the material
    • 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
    • B01F33/05—Mixers using radiation, e.g. magnetic fields or microwaves to mix the material
    • B01F33/054—Mixers using radiation, e.g. magnetic fields or microwaves to mix the material the energy being in the form of a laser to modify the characteristics or conditions of the products, e.g. for heating
    • 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
    • B01F33/302—Micromixers the materials to be mixed flowing in the form of droplets
    • B01F33/3021—Micromixers the materials to be mixed flowing in the form of droplets the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
    • 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
    • B01F33/3033—Micromixers using heat to mix or move the fluids
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0673—Handling of plugs of fluid surrounded by immiscible fluid
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/14—Process control and prevention of errors
    • B01L2200/142—Preventing evaporation
    • 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
    • B01L2300/1861—Means for temperature control using radiation
    • 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
    • B01L2400/0403—Moving fluids with specific forces or mechanical means specific forces
    • B01L2400/0442—Moving fluids with specific forces or mechanical means specific forces thermal energy, e.g. vaporisation, bubble jet
    • 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
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
    • G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
    • G01N2035/1027—General features of the devices
    • G01N2035/1034—Transferring microquantities of liquid
    • G01N2035/1046—Levitated, suspended drops

Definitions

  • the invention relates generally to optical microfluidics. More particularly, the invention relates to an apparatus and method for moving micro-droplets using laser-induced thermal gradients.
  • Microfluidics devices have become a potential source of hope in meeting the needs for high-throughput measurements. Microfluidics possesses the potential for high throughput, rapid reaction ldnetics, and small sample consumption. Industry has produced many types of microfluidic devices, typically using electrophoretic or electroosmotic forces to move small fluid volumes. Current approaches to microfluidic control include lateral flow structures, electrophoretic methods, and pneumatic designs. Each of these approaches has certain limitations that have slowed the pace of microfluidics-device development, such as problems with scaling, assay reconfigurations, poor sample-use efficiency, and considerable complexity of circuitry.
  • Electrophoretic methods for controlling the flow of fluid are not compatible with many solvents, and can result in the separation of biological molecules during steps when solution homogeneity is desired. Further, voltage leakage between microfluidic channels can limit the precision with which the methods can control the flow of fluid. Pneumatic designs have been successfully implemented using soft-lithography techniques, but these implementations are limited to elastomer materials that are not compatible with many types of biological assays. Some lithographic methods produce fixed networks of microconduits (i.e., micropipes) that make reconfiguration difficult and, in effect, result in single-use devices. There is, therefore, a need for microfluidics apparatus and techniques that can avoid or mitigate the aforementioned disadvantages of such current approaches.
  • the invention features a method of moving droplets.
  • a liquid phase is provided on a surface.
  • a droplet is dispensed into the liquid phase, which is immiscible with the droplet.
  • a beam of light is focused at an edge of the droplet in the immiscible liquid phase to produce a thermal gradient sufficient to induce the droplet to move.
  • the invention features an apparatus for moving droplets.
  • the apparatus includes a surface and a droplet disposed on the surface.
  • a light source produces a focused beam of light.
  • the apparatus also includes means of directing the light beam at the droplet disposed on the surface. The light beam heats the droplet to cause a thermal gradient to form across the droplet sufficient to induce the droplet to move across the surface.
  • FIG. 1 is a diagram of an embodiment of an apparatus for optically moving droplets using a focused laser beam in accordance with the invention.
  • FIG. 2 is a diagram illustrating an example of a contact angle formed between a droplet and a surface.
  • FIG. 3A, FIG. 3B, FIG. 3C, and FIG. 3D are an exemplary sequence of images corresponding to the movement and mixing of droplets in accordance with the principles of the invention.
  • FIG. 4 is a diagram illustrating an embodiment of three-fluid system for use in moving droplets using a laser beam in accordance with the invention.
  • FIG. 5 is a flow diagram of an embodiment of a process for optically moving droplets in accordance with the invention.
  • the present invention features methods, apparatus, and microfluidics devices for optically moving micro-droplets using laser-induced thermal gradients.
  • micro means generally a very small amount, i.e., microscale, and does not refer to any particular precise measure (i.e., one-millionth of a unit).
  • Deposited on a surface of a substrate are one or more micro-droplets.
  • a substrate as used herein, generally refers to any material having a surface onto which one or more micro- droplets may be deposited and across which such droplets may be moved.
  • substrate can also refer to a particular substance (e.g., carried within a droplet) upon which an enzyme acts.
  • a liquid phase immiscible with the liquid of the droplets, surrounds the droplets (e.g., to prevent evaporation of the droplets and to improve a contact angle between the droplets and the surface).
  • the immiscible liquid phase may be comprised of multiple, different liquids of different densities that produce a fluid-to-fluid interface at which the droplets are suspended.
  • a laser beam Directed at or near an edge of a selected droplet, a laser beam produces a thermal gradient either across the droplet or within the surrounding liquid phase (or both). The composition of the droplet, liquid phase, and wavelength of the laser beam cooperate to determine where the thermal gradient forms.
  • the thermal gradient caused by the laser beam induces a surface energy or surface tension gradient on the surface of the droplet sufficient to move the droplet in accordance with the Marangoni effect.
  • Surface tension forces produced by the invention are capable of moving droplets of sizes ranging from 1.7 ⁇ L to 14 pL in volume at speeds approximating 3 mm/s. Examples of applications for the present invention include identification of genes, protein- detection assays, single-cell analysis, combinatorial chemistry, and drug development and screening. Exemplary implementations of protection-detection assays are described in United States Patent No. 6,815,210, issued November 9, 2004 to Profitt et al; of identification of a gene, in United State Patent No.
  • Advantages of the present invention include: (1) droplets are dispensable on demand; (2) assays are dynamically reconfigurable; (3) random access to sites on a microfluidic device is possible; and (4) microfluidic devices (substrates) embodying the invention are generally disposable, not requiring expensive or time-consuming fabrication.
  • the present invention also dispenses with features typically needed by other microfluidic techniques, such as valves and pumps, "on-chip” optical and electrical circuitry, and the use of laser pulses in order to fuse droplets.
  • FIG. 1 shows an embodiment of an apparatus 4 for controlling the movement of droplets in accordance with the principles of the invention.
  • the apparatus 4 includes a surface 8 of a substrate 10, an immiscible, non-volatile liquid 12 disposed on the surface 8, and a droplet 14 surrounded by the liquid 12. If the liquid 12 is volatile, means is provided to mitigate evaporation of this liquid such as the use of a cover over the liquid.
  • the droplet 14 is immersed fully in the liquid 12, but full immersion is not required to practice the invention.
  • the droplet is formed from an aqueous fluid (e.g., water and a buffered saline).
  • the droplet 14 can contain other compounds, such as biomolecules (e.g., nucleotidic or peptidic) and surfactants (e.g., anionic, cationic, nonionic, or amphoteric). In practice, the droplet 14 can range in size from approximately 30 ⁇ m to 1500 ⁇ m in diameter.
  • biomolecules e.g., nucleotidic or peptidic
  • surfactants e.g., anionic, cationic, nonionic, or amphoteric.
  • the droplet 14 can range in size from approximately 30 ⁇ m to 1500 ⁇ m in diameter.
  • the surface 8 upon which the droplet 14 is disposed is substantially planar, although the surface 8 may have any contour suitable for microfluidic movement.
  • the substrate 10 can have one of a variety of forms, e.g., wafer, slides, plates, or a standard polystyrene Petri dish.
  • An exemplary implementation of the substrate 10 is a microfluidics device (or "lab-on-a- chip"), such as the microfluidics device described in U.S. Patent No. 6,734,436, issued to Fails et al. on May 11, 2004, and which is incorporated by reference herein.
  • this liquid 12 includes 1-decanol (i.e., an organic liquid). Saturating the liquid 12 beforehand with water can sufficiently slow any aqueous dissolution of the droplet 14 into the surrounding fluid 12.
  • a light source 26 emits a light beam 28.
  • the light source 26 includes a near-infrared (NLR) laser (e.g., 30 mW) that generates an infrared laser beam with a 1550 nm wavelength. This wavelength can operate to heat an aqueous droplet or the surrounding liquid 12 through the vibrational excitation of the first overtone/combination band of the O-H stretch vibration in water.
  • the water O-H vibrational absorption can absorb approximately 10% of this infrared light.
  • the light source 26 includes an Argon ion laser (e.g., 10-200mW) for producing a visible (i.e., green light) laser beam.
  • the droplet 14 or the surrounding liquid 12 (depending upon which is to form a thermal gradient) includes dye - e.g., FD&C Red No. 40, McCormick & Co., Inc. - to produce optical absorption of the laser beam and, as a result, to generate heat through the electronic excitation of the dye molecules.
  • the apparatus 4 also includes a second light source 30 for use, in general, in embodiments where the first light source 26 emits light that is invisible to the unaided human eye.
  • the second light source 30 produces a visible light beam 32, which, when overlapped with the first light beam 28, enables a technician to track visually the position of the invisible light beam 28.
  • the second light source 30 includes a HeNe laser for generating a visible laser beam at a 633 nm wavelength.
  • Cold mirrors 34a and 34b operate to align the light beams 28, 32 to produce a composite light beam 36.
  • Cold mirror 34c directs the light beam 36 to an aspheric lens 38 (with, e.g., a 7 mm aperture).
  • the lens 38 focuses the composite light beam 36 onto the imaging plane of an inverted microscope stage (i.e., that is supporting the substrate 10).
  • the light beam 36 is incident upon the surface 8 from below (i.e., through the substrate 10), and the substrate 10 is transparent to the particular wavelength(s) of the light beam 36.
  • the composite light beam 36 can be directed to the droplet 14 or liquid 12 from above the surface 8 (i.e., not through the substrate 10), without departing from the principles of the invention.
  • a motorized steering mirror 42 situated in the path of the light beam 36 controls the position of the light beam 36 on the image plane of the inverted microscope stage. Faster motion of the laser beam 36 can be achieved using non-mechanical means of steering the laser such as acoustooptic, electrooptic, or liquid crystal devices.
  • the position of the laser beam 36 relative to the droplet 14 may also be controlled by moving the microscope stage.
  • a cold mirror 34d directs images of droplet movement induced by the light beam 36 to a camera 46 connected to a computer system 50.
  • a technician can use this same optical system for controlling the light beam 36 and for observing reactions between fused droplets.
  • FIG. 2 shows the droplet 14 (e.g., immersed in decanol) in contact with a solid surface 66 of a substrate 68.
  • the droplet 14 may touch the surface 66 directly or indirectly (i.e., through the liquid 12).
  • An angle 70 (EJ) forms where the droplet 14 contacts the solid surface 66 is an indicator of the strength of adhesion of the droplet 14 to the surface 66.
  • contact angles of the droplet 14 generally approach 180°, with a small percentage of the droplet perimeter contacting the surface (less than 10% of the droplet diameter). Such large contact angles correspond to low surface adhesion.
  • contact angles on opposite edges of the droplet are symmetric.
  • contact angle hysteresis When applied to the droplet 14, breaks the symmetry between the contact angles, causing a difference between the advancing and receding contact angles, referred to as contact angle hysteresis.
  • the force needed to move the droplet 14 increases with contact angle and contact angle hysteresis.
  • a low contact angle hysteresis facilitates droplet movement.
  • the present invention uses surface tension to move droplets. Surface tension and surface energy generally decrease as temperature increases. Droplets move toward colder regions of the surface where the surface energy is higher, an effect called the thermal Marangoni effect. When the light beam 36 tangentially touches or passes through the droplet 14, a thermal gradient forms across the droplet 14.
  • the droplet 14 heats, for example, by the vibration of O-H stretch of water or the excitation of dye molecules in a dye-carrying droplet. Calculations show that the temperature rise across the width of the droplet 14 is at most approximately 10° C, which should not affect chemical kinetics or the stability of thermally sensitive molecules in a droplet assay.
  • the light-to-dark shading of the droplet 14 provides a graphical illustration of the thermal gradient, the lighter-colored regions of the droplet representing the warmer portions of the temperature gradient, the darker-colored regions representing the cooler portions. This temperature gradient induces a surface energy gradient sufficient to move the droplet 14 in accordance with the Marangoni effect.
  • FIGs. 3 A through 3D provide a sequence of diagrams illustrating an exemplary application of the present invention for a chemical assay.
  • the diagrams correspond to a sequence of video frames produced by a camera (such as camera 46 of FIG. 1). Each image is a view of the droplet motion and mixing from below the substrate 10.
  • a first droplet 80 contains an enzyme, e.g., horseradish peroxidase, in phosphate buffer (0.1 M pH 6.2), and a second droplet 84 contains an excess of chromogenic substrates: 2,2'-azino-bis(3- ethylbenzthiazoline-6-Sulfonic acid) diammonium salt (ABTS), and hydrogen peroxide.
  • an enzyme e.g., horseradish peroxidase
  • phosphate buffer 0.1 M pH 6.2
  • ABTS 2,2'-azino-bis(3- ethylbenzthiazoline-6-Sulfonic acid) diammonium salt
  • the laser beam 88 induces the droplet 80 to move towards the second droplet 84 in accordance with to the Marangoni effect, as described above.
  • Arrow 92 identifies the direction of droplet motion.
  • Line 96 provides a scale for the size of the droplets 50, 84, representing 250 ⁇ m.
  • Droplet volume is conserved the droplets 80, 84, as shown in FIG. 3C.
  • FIG. 3C In FIG.
  • the HRP enzyme in the first droplet 80 reacts with the substrates in the second droplet 84, oxidizing the ABTS and resulting in the darker-colored droplet 98 (i.e., dark green). Reactions are observed in droplets having diameters as small as 40 ⁇ m and at concentrations of approximately 3.7 ⁇ M, which corresponds to approximately 125 attomoles of reacting enzyme. Detection of zeptomoles of reacting enzymes may be attainable by reducing droplet diameter. This same colorization - serving as an indicator of a reaction - also occurs if the laser beam 88 is used to move instead the second droplet 84 into contact with the first droplet 80. This reciprocal observation suggests that moving the first droplet 80 using the laser beam does not heat the contents of the droplet 80 beyond an irreversible denaturing point of the HRP enzyme.
  • a characteristic velocity for the mixing process can be defined by equating the change in surface energy from droplet fusion to the kinetic energy of the droplet volume. This velocity scales as D 1 2 , where D is the droplet diameter; the Reynolds number scales D 1 2 . Observations of the dynamics of merging droplets show contact surface velocities similar to this characteristic velocity.
  • the characteristic velocity is approximately 50 cm/s, corresponding to a Reynolds number of approximately 70.
  • Reynolds numbers greater than approximately two are sufficient for the formation of vortices. Since the flow over a cylinder and the oscillations of coalescing droplets each involves direction- changing flow, the formation of vortices may be occurring during the droplet-fusing process, and the convective motions of such vortices would enhance the mixing process.
  • FIG. 4 shows an embodiment of a system 100 that can be used to avoid contact between the droplet 14 and the surface 8 of the substrate 10 (which may be desirable in order to avoid bio-fouling of the droplet contents with the surface).
  • a standard polystyrene Petri dish 102 holds a liquid phase 106 comprised of a first immiscible liquid 104 and a second immiscible liquid 108.
  • the second immiscible liquid 108 has a greater density than the first immiscible liquid 104 and produce a fluid-to-fluid interface 112 upon which the droplet 14 rests when deposited in the liquid phase.
  • the droplet 14 is suspended above the bottom surface 114 of the Petri dish 102 within the liquid phase 106.
  • the first immiscible liquid 104 is 1-decanol and the second immiscible liquid 108 is perflourinated silicone oil.
  • This system 100 does not exhibit a contact angle hysteresis, thus reducing the force needed to move droplets along the fluid-to-fluid interface 112.
  • Dedicated optical traps or electrostatic trapping techniques can be used (in conjunction with the droplet movement techniques of the present invention) to overcome any convection currents or thermal Brownian motion that may affect precise droplet control.
  • FIG. 5 shows a process 150 for optically performing microfluidic operations, such as * moving, fusing, and mixing micro-droplets, in accordance with the principles of the invention.
  • the particular numbering of the steps of the process 150 does not necessarily imply any particular order in the performance of these steps.
  • a liquid phase comprised of one or more immiscible liquids.
  • prepared and readied for use are the fluids to be manipulated, e.g., samples and reagents, in accordance with the invention.
  • preparation can entail determining the particular composition of the various samples and various reagents and depositing these fluids in respective sample and reagent wells on a microfluidic device or lab-on-a-chip.
  • deposited into the liquid phase are one or more droplets.
  • Such droplets can be samples and reagents drawn from respective wells of a microfluidic device.
  • Examples of techniques for depositing a droplet onto the surface include using a 34-gauge needle (100-micron inner diameter) and directly injecting the droplet from a standard inkjet print head. Other techniques can include the use of printing pins, pipettes, and/or syringes.
  • a laser beam focused adjacent to an edge of one of the droplets on the surface is a laser beam.
  • the laser beam may pass through the droplet, causing the droplet to heat (e.g., through optical absorption of molecules within the droplet or vibration of the water O-H stretch). This heating causes a thermal gradient forms across the droplet, which produces a surface tension across the droplet surface that induces the droplet to move.
  • the laser beam does ⁇ not pass through the droplet, but passes near the droplet such that the thermal gradient produced in the surrounding liquid phase is sufficient to induce the droplet to move.
  • maintaining focus of the laser beam adjacent to the rear (i.e., receding) edge of the droplet steers (step 170) the droplet in a desired direction.
  • the droplet can be moved into a given mixing well of the microfluidic device (to fuse with a droplet already in the well or with a droplet to be moved subsequently into the well).
  • Each well needs not be an actual physical well.
  • the restraining force of contact angle hysteresis may define the location of a well, once the laser is no longer moving the droplet.
  • Microfluidics devices of the invention have a plurality of such mixing wells (e.g., arranged in a two-dimensional array) to enable personnel to perform parallel assays.
  • Heating droplets may be used to perform other functions.
  • thermal cycling is used to perform amplification of DNA
  • laser heating may be used to perform the heating for PCR.
  • Heating without moving the droplet may be achieved by using a laser beam with a hole at the center (a "doughnut" beam). Positioning the laser beam so that the position of the droplet is at the hole in the laser beam results in a situation where the droplet cannot move. Turning the laser beam on and off, repetitiously, results in thermal cycling. The power of the laser and the period for which the laser beam is on control the temperature reached in the droplet.
  • the doughnut beam shape may also be achieved by moving the steering means (42 in Figure 1) in a circular fashion at a faster rate than the droplet can move.

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  • Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Dispersion Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Optics & Photonics (AREA)
  • Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Hematology (AREA)
  • Clinical Laboratory Science (AREA)
  • Apparatus Associated With Microorganisms And Enzymes (AREA)
  • Physical Or Chemical Processes And Apparatus (AREA)
  • Sampling And Sample Adjustment (AREA)

Abstract

La présente invention a trait à un appareil et un procédé de déplacement de micro-gouttelettes. Une phase liquide se trouve sur une surface. Dans la phase liquide se trouve une gouttelette. Un faisceau lumineux se trouve focalisé au niveau d'un bord de la gouttelette. Le faisceau lumineux produit un gradient thermique suffisant pour induire le déplacement de la gouttelette selon l'effet de Marangoni. Le gradient thermique d'induction de déplacement peut apparaître au sein de la gouttelette ou au sein de la phase liquide. La composition de la gouttelette, la phase liquide, et la longueur d'onde du faisceau lumineux peuvent coopérer pour entraîner un réchauffement au sein de la gouttelette, de la phase liquide, ou des deux. Par exemple, un laser infrarouge peut entraîner une vibration d'une liaison O-H dans une gouttelette aqueuse (ou dans la phase liquide). Dans un autre mode de réalisation, l'ajout de colorant à une gouttelette ou à la phase liquide permet l'absorption de la lumière en provenance d'un laser à argon ionisé. L'appareil et le procédé sont particulièrement applicables dans des dosages biologiques et chimiques à haut rendement.
PCT/US2005/002033 2004-01-23 2005-01-21 Appareil et procede de deplacement de micro-gouttelettes au moyen de gradients thermiques induits par laser Ceased WO2005069964A2 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
US10/597,372 US7582858B2 (en) 2004-01-23 2005-01-21 Apparatus and method of moving micro-droplets using laser-induced thermal gradients

Applications Claiming Priority (2)

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US53895104P 2004-01-23 2004-01-23
US60/538,951 2004-01-23

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WO2005069964A2 true WO2005069964A2 (fr) 2005-08-04
WO2005069964A3 WO2005069964A3 (fr) 2005-09-22

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EP1936369A1 (fr) * 2006-12-20 2008-06-25 Agilent Technologies, Inc. Excitation sélective de solvants contenant des radicaux OH
US8293339B2 (en) * 2007-09-17 2012-10-23 Sri International, Inc. Droplet bilayers
EP2574401A1 (fr) * 2006-05-30 2013-04-03 Centre National de la Recherche Scientifique Procédé de fusion de gouttes dans un circuit microfluidique

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US5275787A (en) * 1989-10-04 1994-01-04 Canon Kabushiki Kaisha Apparatus for separating or measuring particles to be examined in a sample fluid
DE4330412A1 (de) * 1993-09-08 1995-03-09 Boehringer Mannheim Gmbh Verfahren und Vorrichtung zur Dosierung von Flüssigkeiten
US20020001544A1 (en) * 1997-08-28 2002-01-03 Robert Hess System and method for high throughput processing of droplets
US6620620B1 (en) * 1998-04-27 2003-09-16 Era Systems, Inc. Micro liquid evaporator
JP2003098068A (ja) * 2001-09-25 2003-04-03 Hitachi Ltd 平面型セル及びそれを用いた分析装置
US20040191127A1 (en) * 2003-03-31 2004-09-30 Avinoam Kornblit Method and apparatus for controlling the movement of a liquid on a nanostructured or microstructured surface

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2574401A1 (fr) * 2006-05-30 2013-04-03 Centre National de la Recherche Scientifique Procédé de fusion de gouttes dans un circuit microfluidique
EP1936369A1 (fr) * 2006-12-20 2008-06-25 Agilent Technologies, Inc. Excitation sélective de solvants contenant des radicaux OH
US8293339B2 (en) * 2007-09-17 2012-10-23 Sri International, Inc. Droplet bilayers

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