WO2009061372A1 - Systèmes et procédés pour créer des entités polyphasiques, comprenant des particules et/ou des fluides - Google Patents

Systèmes et procédés pour créer des entités polyphasiques, comprenant des particules et/ou des fluides Download PDF

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Publication number
WO2009061372A1
WO2009061372A1 PCT/US2008/012384 US2008012384W WO2009061372A1 WO 2009061372 A1 WO2009061372 A1 WO 2009061372A1 US 2008012384 W US2008012384 W US 2008012384W WO 2009061372 A1 WO2009061372 A1 WO 2009061372A1
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Prior art keywords
phase
article
entity
particles
average diameter
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PCT/US2008/012384
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English (en)
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WO2009061372A9 (fr
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Rhutesh Kishorkant Shah
Jin-Woong Kim
David A. Weitz
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President And Fellows Of Harvard College
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Publication of WO2009061372A1 publication Critical patent/WO2009061372A1/fr
Publication of WO2009061372A9 publication Critical patent/WO2009061372A9/fr

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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K23/00—Use of substances as emulsifying, wetting, dispersing, or foam-producing agents
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K23/00—Use of substances as emulsifying, wetting, dispersing, or foam-producing agents
    • C09K23/16—Amines or polyamines
    • C—CHEMISTRY; METALLURGY
    • C09—DYES; PAINTS; POLISHES; NATURAL RESINS; ADHESIVES; COMPOSITIONS NOT OTHERWISE PROVIDED FOR; APPLICATIONS OF MATERIALS NOT OTHERWISE PROVIDED FOR
    • C09K—MATERIALS FOR MISCELLANEOUS APPLICATIONS, NOT PROVIDED FOR ELSEWHERE
    • C09K23/00—Use of substances as emulsifying, wetting, dispersing, or foam-producing agents
    • C09K23/22—Amides or hydrazides

Definitions

  • the present invention generally relates to multi-phase entities, which may include one or more phases containing particles.
  • the particles may be agglomerated.
  • the present invention generally relates to multi-phase entities, which may include one or more phases containing particles.
  • the particles may be agglomerated in some cases.
  • the subject matter of the present invention involves, in some cases, interrelated products, alternative solutions to a particular problem, and/or a plurality of different uses of one or more systems and/or articles.
  • the invention relates to an article.
  • the article comprises a multi-phase entity comprising at least a first phase and a second phase, wherein at least one of the phases comprises colloidal particles, and at least some of the colloidal particles have a first hydrophobicity/hydrophilicity at a first temperature and a second hydrophobicity/hydrophilicity different from the first hydrophobicity/hydrophilicity at a second temperature.
  • the article comprises a multi-phase entity comprising at least a first phase and a second phase, wherein at least one of the phases comprises colloidal particles, and at least some of the colloidal particles have a first hydrophobicity/hydrophilicity at a first pH and a second hydrophobicity/hydrophilicity different from the first hydrophobicity/hydrophilicity at a second pH.
  • the article in yet another embodiment, comprises a multi-phase entity comprising at least a first phase and a second phase, wherein at least one of the phases comprises colloidal particles, and at least some of the colloidal particles are able to bind to an analyte.
  • the article comprises a multi-phase entity having a maximum dimension of no more than about 1 mm, wherein the multi -phase entity comprises at least three phases, and at least one phase is defined by an agglomeration of sub-particles.
  • the article comprises an outer fluid droplet containing one or more first fluid droplets, at least one of which contains one or more second fluid droplets, wherein at least one of the second fluid droplets contains agglomerated particles.
  • the article comprises a fluid droplet containing more than one nesting level of inner fluid droplets therein, wherein a nesting level is defined by one or more fluid droplets each contained within a surrounding fluid droplet, and wherein at least one nesting level is defined by an agglomeration of particles.
  • the article comprises a microparticle containing a first phase surrounding a second phase, wherein the second phase is defined by an agglomeration of sub-particles, according to another embodiment.
  • the article comprises a microparticle containing at least three phases with one of the phases surrounding the other phases, and at least one of the phases is defined by an agglomeration of sub-particles.
  • the article in yet another embodiment, comprises a particle having a first, generally hemispherical phase and a second, generally hemispherical phase, wherein the second generally hemispherical phase is porous.
  • the method comprises providing a multi-phase entity comprising at least a first phase and a second phase, and altering the hydrophobicity/hydrophilicity of the first phase by altering the temperature of the multi-phase entity.
  • the method comprises providing a multi-phase entity comprising at least a first phase and a second phase, and altering the hydrophobicity/hydrophilicity of the first phase by altering pH, according to another embodiment of the invention.
  • the method comprises providing a fluid containing an emulsion defined by a continuous and a discontinuous phase defined by a plurality of fluid droplets, and solidifying at least a portion of the discontinuous phase without solidifying the continuous phase.
  • the method in another embodiment, comprises providing emulsified fluid droplets, each droplet defined by a continuous and a discontinuous phase, condensing the discontinuous phase in each fluid droplet in one portion of the fluid droplet, and polymerizing the continuous phase in each fluid droplet.
  • FIGS. 1 A-IC illustrate the agglomeration of microgels according to one set of embodiments of the invention
  • FIGS. 2A-2E illustrate the method of producing articles according to one set of embodiments of the invention
  • FIG. 3 is a photograph of a microreactor used to produce articles according to one set of embodiments of the invention.
  • FIGS. 4A-4E are a series of micrographs showing articles according to one set of embodiments of the invention.
  • FIG. 5 is a schematic illustrating a method of producing articles according to one set of embodiments of the invention.
  • FIGS. 6A-6B are plots illustrating the dependence of a property of an article on system parameters according to one set of embodiments of the invention
  • FIGS. 7A-7E are schematics of methods of producing articles and resultant articles according to one set of embodiments of the invention.
  • FIGS. 8A-8B are micrographs of articles according to one set of embodiments of the invention.
  • FIGS. 9A-9C are confocal images illustrating the effect of a system parameter on an article property according to one set of embodiments of the invention.
  • FIGS. 10A- 1OB are (A) a micrograph and (B) a confocal image of an article according to one set of embodiments of the invention.
  • FIGS. 1 IA-I IE are micrographs of an article according to one set of embodiments of the invention.
  • FIG. 12 is a schematic representation of a set of embodiments used to make particles;
  • FIGS. 13A-13C illustrate particles formed by photopolymerizing monomers in phase separated droplets according to one set of embodiments
  • FIGS. 14A-14B illustrate closely packed microgels forming a raspberry-like structure, according to one set of embodiments
  • FIG. 15A-15B illustrate the swelling kinetics of a PNIPAm phase within a droplet upon cooling to room temperature, according to one set of embodiments
  • FIG. 16 is a photograph illustrating the behavior of magnetic particles, according to one set of embodiments
  • FIG. 17 is a fluorescent microscope image displaying an array of microgels synthesized by precipitation polymerization, according to one set of embodiments;
  • FIG. 18A-18B illustrate capillary based microfluidic device that uses flow focusing geometry, according to one set of embodiments;
  • FIG. 19 includes a micrograph of a microfluidic device used to generate droplets, according to one set of embodiments.
  • the present invention generally relates to multi-phase entities, which may include one or more phases containing particles.
  • the particles may be agglomerated in some cases.
  • the multi-phase entity contains one or more phases and/or regions, which each may independently be a solid or a liquid.
  • a multi- phase entity may contain a solid phase and a liquid phase, a first solid phase and a second solid phase, a first liquid phase and a second liquid phase, etc., and the phases may be present within one or more regions within the entity.
  • the hydrophobicities/hydrophilicities of one or more phases of the multi-phase entity are sensitive to temperature, pH, and/or an analyte, etc.
  • Still other aspects of the invention generally relate to systems and methods of making and using such multi -phase entities, kits involving such entities, or the like.
  • Fields in which various multi-phase entities of the present invention may be useful include (but are not limited to), for example, food, beverage, health and beauty aids, paints and coatings, chemical separations, and drugs and drug delivery.
  • a precise quantity of a drug, pharmaceutical, or other agent can be contained within an entity by a phase designed to release its contents under particular conditions, as described in detail below.
  • Other species that can be stored and/or delivered in an entity include, for example, biochemical species such as nucleic acids such as RNA or DNA, proteins, peptides, or enzymes.
  • multi-phase entity is an entity containing a least a first phase and a second phase, and in some cases, a third phase, a fourth phase, etc.
  • the "phases" will have distinct chemical and/or physical properties. For instance, each of the phases may independently be a solid or a fluid such as a liquid.
  • the multi-phase entity may contain a solid phase and a liquid phase, a first solid phase and a second solid phase, a first liquid phase and a second liquid phase, etc.
  • FIG. IB shows a multi-phase entity having a liquid phase and a solid phase.
  • FIGS. 4A-4B show a collection of multi-phase entities having a first solid phase and a second solid phase.
  • the phases may be positioned in any location within the multi-phase entity, for example, one phase may be surrounded by a second phase (e.g. as shown in FIGS.
  • two phases may be positioned side-by-side (for example, as in a Janus particle, where each phase has a generally hemispherical shape, e.g., as is shown in FIG. IB, or the like).
  • multiple phases may be nested, as discussed below.
  • a combination of these and/or other phases may be present within the multi-phase entity.
  • the multi-phase entity has a maximum dimension of no more than about 1 mm. In other cases, the multi-phase entity may have a maximum dimension of less than about 500 micrometers, less than about 300 micrometers, less than about 100 micrometers, less than about 10 micrometers, or less than about 1 micrometer or smaller, in some cases.
  • one or more phases of a multi -phase entity may be present as a single continuous region, or as multiple, discrete regions within the multi-phase entity.
  • a multi-phase entity may be droplet containing an emulsion therein (e.g., such that the continuous phase of the emulsion is the first phase, and the discontinuous phase of the emulsion is the second phase, present as a plurality of discrete regions contained within the first phase).
  • a multi-phase entity may be a droplet or a particle containing (sub-)particles, as discussed below, where the (sub-)particles define a phase within the entity.
  • the (sub-)particles may be present as discrete particles (thereby defining discrete regions within the droplet or particle), and/or as one or more agglomerations of particles.
  • a plurality of sub-particles may be agglomerated or immobilized relative to each other in some fashion, thereby defining a solid phase within the multi-phase entity.
  • the multi-phase entity may be created using a microfluidic system. Non-limiting examples of such a system are shown in FIGS. 3, 4A- 4B, and 8A-8B.
  • FIG. 2 A schematically illustrates the creation of multi -phase entities in a microfluidic system, according to one embodiment of the invention.
  • an aqueous emulsion phase containing PNIPAM poly(N-isopropyl acrylamide)), PAA (poly(acrylic acid)), acrylamide, a crosslinker, and a photoinitiator are fed into a capillary channel.
  • the aqueous phase in this example, is surrounded by a continuous phase of silicon oil (e.g., DC550 from Dow Corning). Downstream of the inlet, phase separation of the emulsion is induced by, for example, heating the system. Upon phase separation, the PNIPAM may form an agglomerated microgel which can condense to one side of the multi-phase entity.
  • the residual polymer in the aqueous phase may be polymerized, forming a multi-phase entity where the two phases are positioned side-by-side.
  • This technique can produce multi-phase entities such as the examples shown in FIGS. 2C-2E. In other embodiments, however, a microfluidic system is not necessary to create the multi-phase entities.
  • One aspect of the present invention is generally directed to multi -phase entities having at least three phases.
  • the phases may be positioned in any orientation within the entity relative to each other. For instance, one of the phases may surround the other phases.
  • the multi-phase entity may be created from multiple emulsions such as those described in International Patent Application No. PCT/US2006/007772, filed March 3, 2006, entitled “Method and Apparatus for Forming Multiple Emulsions," published as WO 2006/096571 on September 14, 2006 or U.S. Provisional Patent Application Serial No. 60/920,574, filed March 28, 2007, entitled “Multiple Emulsions and Techniques for Formation,” each incorporated herein by reference, and may include any number of phases, which may be side-by-side or nested in some cases.
  • an entity may contain one, two, three, four, or more phases therein, some or all of which can contain additional phases therein.
  • a first phase may contain a second phase, which may contain a third phase, etc.
  • a nesting level can be defined by one or more phases each contained within a surrounding phase.
  • one phase may be present within a multi-phase entity as a plurality of discrete regions, e.g., as a plurality of droplets, particles, or the like. Any of these may be of substantially the same shape and/or size (i.e., "monodisperse"), or of different shapes and/or sizes, depending on the particular application. For instance, the droplets, particles, etc.
  • the droplets may have a homogenous distribution of diameters, i.e., having a distribution of diameters such that no more than about 10%, about 5%, about 3%, about 1%, about 0.03%, or about 0.01% of the droplets have an average diameter greater than about 10%, about 5%, about 3%, about 1%, about 0.03%, or about 0.01% of the average diameter.
  • the "average diameter" of a plurality or series of droplets or particles is the arithmetic average of the average diameters of each of the droplets or particles. Those of ordinary skill in the art will be able to determine the average diameter (or other characteristic dimension), for example, using laser light scattering, microscopic examination, or other known techniques.
  • the average diameter of a single entity, in a non-spherical entity is the diameter of a perfect sphere having the same volume as the non-spherical entity.
  • the average diameter may be, for example, less than about 1 mm, less than about 500 micrometers, less than about 200 micrometers, less than about 100 micrometers, less than about 75 micrometers, less than about 50 micrometers, less than about 25 micrometers, less than about 10 micrometers, or less than about 5 micrometers in some cases.
  • the average diameter may also be at least about 1 micrometer, at least about 2 micrometers, at least about 3 micrometers, at least about 5 micrometers, at least about 10 micrometers, at least about 15 micrometers, or at least about 20 micrometers in certain cases.
  • fluid generally refers to a substance that tends to flow and to conform to the outline of its container, i.e., a liquid, a gas, a viscoelastic fluid, etc.
  • fluids are materials that are unable to withstand a static shear stress, and when a shear stress is applied, the fluid experiences a continuing and permanent distortion.
  • the fluid may have any suitable viscosity that permits flow. If two or more fluids are present, each fluid may be independently selected among essentially any fluids (liquids, gases, and the like) by those of ordinary skill in the art, by considering the relationship between the fluids.
  • the droplets may be contained within a carrier fluid, e.g., a liquid.
  • a "droplet,” as used herein, is an isolated portion of a first fluid that is surrounded, e.g., by a second fluid or a solid, etc. It is to be noted that a droplet is not necessarily spherical, but may assume other shapes as well, for example, depending on the external environment.
  • two (or more) of the phases within the multi-phase entity may be present as an emulsion or a suspension, e.g., where one phase (the continuous phase) contains a second phase (the discontinuous phase) that is present as discrete regions within the continuous phase.
  • a fluid may contain therein fluidic droplets that form an emulsion with the fluid.
  • Emulsions or multiple emulsions may be formed using techniques such as such as those described in International Patent Application No. PCT/US2006/007772, filed March 3, 2006, entitled “Method and Apparatus for Forming Multiple Emulsions," published as WO
  • a phase defined by particles may be created by solidifying a liquid phase or a discontinuous phase of an emulsion, e.g., to form solid particles.
  • a phase may be defined by a gel, which can be created, for example, by causing gelling of a discontinuous phase of an emulsion.
  • the gel in some cases, may be condensed to form a single phase within the multi-phase entity.
  • a phase may be solidified by reducing the temperature of the phase to a temperature that causes the phase to reach a solid state.
  • Any technique able to solidify a fluid can be used.
  • the phase may be solidified by cooling the phase to a temperature that is below the melting point or glass transition temperature of the phase, thereby causing the phase to become solid.
  • an emulsion may be formed at an elevated temperature (e.g., above room temperature, about 25 0 C), then cooled, e.g., to room temperature or to a temperature below room temperature; an emulsion may be formed at room temperature, then cooled to a temperature below room temperature, or the like.
  • a plurality of regions and/or phases may be solidified to form a plurality of discrete particles, which can be agglomerated in some cases to produce an agglomeration of particles.
  • a phase is solidified using a chemical and/or a polymerization reaction that causes solidification of the phase to occur. For example, two or more fluids may react to produce a solid product, thereby causing formation of a solid phase.
  • a first reactant may be reacted with a second reactant surrounding the fluidic droplet to produce a solid, which may cause a solid "shell” to form in some cases, thereby forming a core/shell structure having a solid shell or exterior, and a fluidic core or interior, e.g., containing liquid or gas.
  • a polymerization reaction may be initiated within a phase, thereby causing the formation of a polymeric particle.
  • the phase may contain one or more monomer or oligomer precursors (e.g., dissolved and/or suspended within the fluidic droplet), which may polymerize to form a polymer that is solid.
  • the polymerization reaction may occur spontaneously, or be initiated in some fashion, e.g., during formation of the phase, or after the phase has been formed.
  • the polymerization reaction may be initiated by adding an initiator to the phase, by applying light or other electromagnetic energy to the phase (e.g., to initiate a photopolymerization reaction), or the like.
  • the phase may comprise a material having a sol state and a gel state (e.g., a hydrogel), such that the conversion of the material from the sol state into a gel state causes the phase to solidify.
  • a material having a sol state and a gel state e.g., a hydrogel
  • the conversion of the sol state of the material within the fluidic droplet into a gel state may be accomplished through any technique known to those of ordinary skill in the art, for instance, by cooling the phase, by initiating a polymeric reaction within the phase, etc.
  • the phase containing the agarose may be produced at a temperature above the gelling temperature of agarose, then subsequently cooled, causing the agarose to enter a gel state.
  • the phase contains acrylamide (e.g., dissolved within the fluidic droplet)
  • the acrylamide may be polymerized (e.g., using tetramethylethylenediamine) to produce a polymeric particle comprising polyacrylamide, for example, as a hollow particle containing a fluid therein.
  • one or more phases of the multi-phase entity may be defined by particles, such as an agglomeration of particles. Any of the phases present within a multi-phase entity may be defined by particles.
  • a multi-phase entity may contain a first phase and a second phase, where the second phase is defined by an agglomeration of sub-particles.
  • the first phase is also solid, i.e., the multi-phase entity is a particle, such as a microparticle.
  • the first phase may surround the second phase (or vice versa), or both phases may be generally hemispherical, e.g., as in a Janus particle, as shown in FIGS.
  • phase may be present within the multi-phase entity, and the phases may be present in any configuration, where at least one of the phases is defined by particles, such as an agglomeration of particles.
  • the agglomeration is porous, e.g., the particles are not connected together as an impenetrable mass, and channels or "pores" may be present within the agglomeration of particles.
  • multi-phase entities comprise one or more phases that comprise colloidal particles.
  • colloidal particles is given its ordinary meaning in the art, and is generally used to refer to a type of mechanical mixture where one substance (e.g., colloidal particles) is dispersed evenly throughout another (e.g., a fluid medium).
  • colloidal particles may refer to particles that form a colloid when dispersed in a medium, such as water.
  • the phases of and/or particles in the multiphase entity have a first hydrophobicity/hydrophilicity at a first temperature and a second hydrophobicity/hydrophilicity at a second temperature. Accordingly, by altering the temperature, the hydrophobicity/hydrophilicity of the multi-phase entity may be altered.
  • the difference between the first temperature and the second temperature is at least about 1 0 C, at least about 5 0 C, at least about 10 0 C, at least about 25 0 C, at least about 50 °C, at least about 100 0 C, or at least about 250 0 C.
  • the hydrophobicity of the phases and/or particles can be measured using techniques known to those of ordinary skill in the art, for example, by the contact angle of a water droplet on a surface coated with the material.
  • Non-limiting examples of materials that exhibit a temperature-dependent hydrophibicity/hydrophilicity include poly(N-isopropyl acrylamide) (PNIPAM) and poly(n-vinylcaprolactam) (PVCL).
  • PNIPAM poly(N-isopropyl acrylamide)
  • PVCL poly(n-vinylcaprolactam)
  • the "hydrophobicity/hydrophilicity” is defined relatively as a material property, i.e., a particle or a phase within the multi-phase entity may have a first hydrophobicity/hydrophilicity at a first temperature and a second hydrophobicity/hydrophilicity at a second temperature.
  • the particle or phase may be hydrophobic relative to water, or hydrophilic relative to water, etc.
  • the hydrophobicity/hydrophilicity at the first temperature may be hydrophobic (relative to water) and the hydrophobicity/hydrophilicity at the second temperature may be hydrophilic, etc.
  • at least some of the particles and/or phases have a first hydrophobicity/hydrophilicity at a first pH and a second hydrophobicity/hydrophilicity at a second pH.
  • the hydrophobicity/hydrophilicity of the multi-phase entity may be altered.
  • the difference between the first pH and the second pH is at least about 0.1, at least about 0.5, at least about 1 , at least about 1.5, at least about 2, at least about 3, at least about 4, at least about 5, or at least about 7, etc.
  • materials that exhibit a pH-dependent hydrophobicity/hydrophilicity are poly(vinyl pyridine), poly(acrylic acid), poly(methacrylic acid), poly(alylamine hydrochloride), and poly(ethyleneimine) .
  • at least some of the particles and/or phases are able to bind to an analyte.
  • the analyte may be one that is able to bind, typically specifically, or otherwise interact with the colloidal particle, or at least a portion thereof.
  • Non-limiting examples include dyes sensitive to pH, temperature, ions, or the like. Examples of such compounds include, but are not limited to, pH-sensitive dyes such as phenol red, bromothymol blue, chlorophenol red, fluorescein, HPTS, 5(6)- carboxy-2',7'-dimethoxyfluorescein SNARP, and phenothalein; dyes sensitive to calcium such as Fura-2 and Indo-1; dyes sensitive to chloride such as 6-methoxy-N-(3- sulfopropyl)-quinolinim and lucigenin; dyes sensitive to nitric oxide such as 4-amino-5- methylamino-2',7'-difluorofluorescein; dyes sensitive to oxygen such as tris(4,4'- diphenyl-2,2'-bipyridine) ruthenium (
  • At least one of the particles and/or phases within a multi -phase entity comprises magnetic and/or charged particles.
  • a multi-phase entity may comprise at least one phase comprising charged particles and, at the same time, at least one phase substantially free of charged particles.
  • the multi-phase entity comprises one or more phase comprising magnetic particles and, at the same time, one or more phase substantially free of magnetic particles.
  • the discontinuous phase of an emulsion used to form a multi-phase entity may be condensed, i.e., to form a separate, continuous phase.
  • the discontinuous phase may be liquid (e.g., forming a new continuous, liquid phase, which may be contained within the continuous phase of the emulsion), or a solid (e.g., forming an agglomeration of particles). Examples of forming a solid discontinuous phase are discussed in detail herein.
  • poly(N- isopropyl acrylamide) PNIPAM
  • PNIPAM microgels may, for example, be synthesized with allyl amine and have NH 2 functionality on the surface.
  • Addition of small amounts of polyacrylic acid to the PNIPAM suspension may cause the PNIPAM microgels to aggregate, e.g., due to electrostatic interactions.
  • the aggregation process can also be accelerated in some cases by heating.
  • the microgels may be heated to about 65 0 C. A schematic of this process is shown in FIG. IA.
  • the condensation of a discontinuous phase of an emulsion to form a separate, continuous phase is induced mechanically.
  • the condensation of a discontinuous phase of an emulsion to form a separate, continuous phase is induced by heating. Condensation can be induced, for example, by heating to temperatures of at least about 20 0 C, at least about 25 0 C, at least about 50 0 C, at least about 100 0 C, or at least about 250 0 C.
  • a continuous phase may be polymerized, e.g., to produce a multi-phase particle.
  • the relative volumes of the continuous and discontinuous phases are controlled by varying the temperature at which the condensation step occurs.
  • the relative volumes of the two phases are controlled by varying the time between the condensation and polymerization steps. In still other embodiments, the relative volumes of the two phases are controlled by varying the chemical composition of the emulsified fluid droplet. In yet other embodiments, combinations of these and/or other techniques can be used.
  • Example 2 includes examples of detailed descriptions of the control of relative volumes using process parameters.
  • multi-phase entities may be formed by flowing two, three, or more fluids through a system of conduits, and optionally solidifying and/or condensing one or more of the fluids.
  • the system may be a microfluidic system.
  • Microfluidic refers to a device, apparatus or system including at least one fluid channel having a cross-sectional dimension of less than about 1 millimeter (mm), and in some cases, a ratio of length to largest cross- sectional dimension of at least 3:1.
  • One or more conduits of the system may be a capillary tube. In some cases, multiple conduits are provided, and in some embodiments, at least some are nested, as described herein.
  • the conduits may be in the microfluidic size range and may have, for example, average inner diameters, or portions having an inner diameter, of less than about 1 millimeter, less than about 300 micrometers, less than about 100 micrometers, less than about 30 micrometers, less than about 10 micrometers, less than about 3 micrometers, or less than about 1 micrometer, thereby providing droplets having comparable average diameters.
  • One or more of the conduits may (but not necessarily), in cross section, have a height that is substantially the same as a width at the same point.
  • Conduits may include an orifice that may be smaller, larger, or the same size as the average diameter of the conduit.
  • conduit orifices may have diameters of less than about 1 mm, less than about 500 micrometers, less than about 300 micrometers, less than about 200 micrometers, less than about 100 micrometers, less than about 50 micrometers, less than about 30 micrometers, less than about 20 micrometers, less than about 10 micrometers, less than about 3 micrometers, etc.
  • the conduits may be rectangular or substantially non-rectangular, such as circular or elliptical.
  • the conduits of the present invention can also be disposed in or nested in another conduit, and multiple nestings are possible in some cases. In some embodiments, one conduit can be concentrically retained in another conduit and the two conduits are considered to be concentric.
  • one conduit may be off-center with respect to another, surrounding conduit.
  • the inner and outer fluids which are typically miscible, may avoid contact, which can facilitate great flexibility in making multi-phase entities such as those described herein.
  • FIG. 19 is a non-limiting example of a micrograph of an apparatus used to make multiple emulsions.
  • a coaxial flow geometry and hydrodynamic focusing are used to produce multiple droplets within a single droplet.
  • Many parameters of the multi-phase entities including both inner droplets and middle layer droplets (outer droplets), can be controlled using hydrodynamic focusing. For instance, droplet diameter, outer droplet volume and the total number of inner droplets per outer droplet can be controlled.
  • the multi-phase entities comprise phases that are miscible. Some embodiments may also comprise multi-phase entities in two or more phases are substantially immiscible.
  • two fluids are "immiscible,” or not miscible, with each other when one is not soluble in the other to a level of at least 10% by weight at the temperature and under the conditions at which the multiple emulsion is produced. For instance, two fluids may be selected to be immiscible within the time frame of a particular technique carried out in accordance with the invention.
  • a "channel,” as used herein, means a feature on or in an article (substrate) that at least partially directs flow of a fluid.
  • the channel can have any cross-sectional shape (circular, oval, triangular, irregular, square or rectangular, or the like) and can be covered or uncovered. In embodiments where it is completely covered, at least one portion of the channel can have a cross-section that is completely enclosed, or the entire channel may be completely enclosed along its entire length with the exception of its inlet(s) and/or outlet(s).
  • a channel may also have an aspect ratio (length to average cross sectional dimension) of at least 2: 1 , more typically at least 3: 1, 5: 1, 10: 1, 15: 1, 20:1, or more.
  • An open channel generally will include characteristics that facilitate control over fluid transport, e.g., structural characteristics (an elongated indentation) and/or physical or chemical characteristics (hydrophobicity vs.
  • hydrophilicity or other characteristics that can exert a force (e.g., a containing force) on a fluid.
  • the fluid within the channel may partially or completely fill the channel.
  • the fluid may be held within the channel, for example, using surface tension (i.e., a concave or convex meniscus).
  • the channel may be of any size, for example, having a largest dimension perpendicular to fluid flow of less than about 5 mm or 2 mm, or less than about 1 mm, or less than about 500 microns, less than about 200 microns, less than about 100 microns, less than about 60 microns, less than about 50 microns, less than about 40 microns, less than about 30 microns, less than about 25 microns, less than about 10 microns, less than about 3 microns, less than about 1 micron, less than about 300 nm, less than about 100 nm, less than about 30 nm, or less than about 10 nm.
  • the dimensions of the channel may be chosen such that fluid is able to freely flow through the article or substrate.
  • the dimensions of the channel may also be chosen, for example, to allow a certain volumetric or linear flowrate of fluid in the channel.
  • the number of channels and the shape of the channels can be varied by any method known to those of ordinary skill in the art. In some cases, more than one channel or capillary may be used. For example, two or more channels may be used, where they are positioned inside each other, positioned adjacent to each other, positioned to intersect with each other, etc.
  • a variety of materials and methods, according to certain aspects of the invention, can be used to form systems (such as those described above) able to produce the multiphase entities.
  • various components can be formed from solid materials, in which the channels can be formed via micromachining, film deposition processes such as spin coating and chemical vapor deposition, laser fabrication, photolithographic techniques, etching methods including wet chemical or plasma processes, and the like. See, for example, Scientific American, 248:44-55, 1983 (Angell, et al).
  • at least a portion of the fluidic system is formed of silicon by etching features in a silicon chip. Technologies for precise and efficient fabrication of various fluidic systems and devices of the invention from silicon are known.
  • various components of the systems and devices of the invention can be formed of a polymer, for example, an elastomeric polymer such as polydimethylsiloxane (“PDMS”), polytetrafluoroethylene (“PTFE” or Teflon®), or the like.
  • PDMS polydimethylsiloxane
  • PTFE polytetrafluoroethylene
  • Teflon® Teflon®
  • Different components can be fabricated of different materials.
  • a base portion including a bottom wall and side walls can be fabricated from an opaque material such as silicon or PDMS
  • a top portion can be fabricated from a transparent or at least partially transparent material, such as glass or a transparent polymer, for observation and/or control of the fluidic process.
  • Components can be coated so as to expose a desired chemical functionality to fluids that contact interior channel walls, where the base supporting material does not have a precise, desired functionality.
  • components can be fabricated as illustrated, with interior channel walls coated with another material.
  • Material used to fabricate various components of the systems and devices of the invention e.g., materials used to coat interior walls of fluid channels, may desirably be selected from among those materials that will not adversely affect or be affected by fluid flowing through the fluidic system, e.g., material(s) that is chemically inert in the presence of fluids to be used within the device.
  • various components of the invention are fabricated from polymeric and/or flexible and/or elastomeric materials, and can be conveniently formed of a hardenable fluid, facilitating fabrication via molding (e.g. replica molding, injection molding, cast molding, etc.).
  • the hardenable fluid can be essentially any fluid that can be induced to solidify, or that spontaneously solidifies, into a solid capable of containing and/or transporting fluids contemplated for use in and with the fluidic network.
  • the hardenable fluid comprises a polymeric liquid or a liquid polymeric precursor (i.e. a "prepolymer").
  • Suitable polymeric liquids can include, for example, thermoplastic polymers, thermoset polymers, or mixture of such polymers heated above their melting point.
  • a suitable polymeric liquid may include a solution of one or more polymers in a suitable solvent, which solution forms a solid polymeric material upon removal of the solvent, for example, by evaporation.
  • a suitable solvent such polymeric materials, which can be solidified from, for example, a melt state or by solvent evaporation, are well known to those of ordinary skill in the art.
  • a variety of polymeric materials, many of which are elastomeric, are suitable, and are also suitable for forming molds or mold masters, for embodiments where one or both of the mold masters is composed of an elastomeric material.
  • a non-limiting list of examples of such polymers includes polymers of the general classes of silicone polymers, epoxy polymers, and acrylate polymers.
  • Epoxy polymers are characterized by the presence of a three- membered cyclic ether group commonly referred to as an epoxy group, 1 ,2-epoxide, or oxirane.
  • diglycidyl ethers of bisphenol A can be used, in addition to compounds based on aromatic amine, triazine, and cycloaliphatic backbones.
  • Another example includes the well-known Novolac polymers.
  • Non-limiting examples of silicone elastomers suitable for use according to the invention include those formed from precursors including the chlorosilanes such as methylchlorosilanes, ethylchlorosilanes, phenylchlorosilanes, etc.
  • Silicone polymers are preferred in one set of embodiments, for example, the silicone elastomer polydimethylsiloxane.
  • Non-limiting examples of PDMS polymers include those sold under the trademark Sylgard by Dow Chemical Co., Midland, MI, and particularly Sylgard 182, Sylgard 184, and Sylgard 186.
  • Silicone polymers including PDMS have several beneficial properties simplifying fabrication of the microfluidic structures of the invention. For instance, such materials are inexpensive, readily available, and can be solidified from a prepolymeric liquid via curing with heat.
  • PDMSs are typically curable by exposure of the prepolymeric liquid to temperatures of about, for example, about 65 °C to about 75 °C for exposure times of, for example, about an hour.
  • silicone polymers such as PDMS
  • PDMS polymethyl methacrylate copolymer
  • flexible (e.g., elastomeric) molds or masters can be advantageous in this regard.
  • One advantage of forming structures such as microfluidic structures of the invention from silicone polymers, such as PDMS, is the ability of such polymers to be oxidized, for example by exposure to an oxygen-containing plasma such as an air plasma, so that the oxidized structures contain, at their surface, chemical groups capable of cross-linking to other oxidized silicone polymer surfaces or to the oxidized surfaces of a variety of other polymeric and non-polymeric materials.
  • an oxygen-containing plasma such as an air plasma
  • oxidized silicone such as oxidized PDMS can also be sealed irreversibly to a range of oxidized materials other than itself including, for example, glass, silicon, silicon oxide, quartz, silicon nitride, polyethylene, polystyrene, glassy carbon, and epoxy polymers, which have been oxidized in a similar fashion to the PDMS surface (for example, via exposure to an oxygen-containing plasma).
  • Oxidation and sealing methods useful in the context of the present invention, as well as overall molding techniques, are described in the art, for example, in an article entitled “Rapid Prototyping of Microfluidic Systems and Polydimethylsiloxane,” Anal. Chem., 70:474-480, 1998 (Duffy, et al.), incorporated herein by reference.
  • certain microfluidic structures of the invention may be formed from certain oxidized silicone polymers. Such surfaces may be more hydrophilic than the surface of an elastomeric polymer. Such hydrophilic channel surfaces can thus be more easily filled and wetted with aqueous solutions.
  • a bottom wall of a microfluidic device of the invention is formed of a material different from one or more side walls or a top wall, or other components.
  • the interior surface of a bottom wall can comprise the surface of a silicon wafer or microchip, or other substrate.
  • Other components can, as described above, be sealed to such alternative substrates. Where it is desired to seal a component comprising a silicone polymer (e.g.
  • the substrate may be selected from the group of materials to which oxidized silicone polymer is able to irreversibly seal (e.g., glass, silicon, silicon oxide, quartz, silicon nitride, polyethylene, polystyrene, epoxy polymers, and glassy carbon surfaces which have been oxidized).
  • materials to which oxidized silicone polymer is able to irreversibly seal e.g., glass, silicon, silicon oxide, quartz, silicon nitride, polyethylene, polystyrene, epoxy polymers, and glassy carbon surfaces which have been oxidized.
  • other sealing techniques can be used, as would be apparent to those of ordinary skill in the art, including, but not limited to, the use of separate adhesives, bonding, solvent bonding, ultrasonic welding, etc. The following are each incorporated herein by reference: U.S. Patent Application
  • FIGS. 2B-2E illustrate a multi-phase entity comprising polymerized polyacrylamide in the first phase and cross-linked poly(N-isopropyl acrylamide) (PNIPAM) aggregate in the second phase.
  • the polyacrylamide was hydrophilic at all temperatures.
  • the cross-linked PNIPAM was hydrophilic at low temperatures (i.e. less than about 32 0 C) and hydrophobic at high temperatures (e.g. greater than about 32 0 C).
  • FIG. 2C shows a PNIPAM suspension in water with polyacrylamide, acrylamide, BIS (a cross-linking agent), and Darocur 1173 (a photoinitiator).
  • the PNIPAM polymerized, aggregated and separated from the polyacrylic acid.
  • the PAA was then crosslinked together, e.g., using ultraviolet light (e.g., as shown schematically in FIG. 2B).
  • the PNIPAM was chemically cross-linked with an aldehyde such as, for example, glutaric aldehyde. Consequently, at temperatures above about 32 0 C, the multi-phase article was amphiphilic and could be used in a surfactant. At temperatures below about 32 0 C, the entire article was hydrophilic.
  • FIG. 2A illustrates the production of multi-phase entities.
  • PNIPAM poly(N-isopropyl acrylamide)
  • PAA poly acrylic acid
  • PAA poly acrylic acid
  • acrylamide a cross-linking agent
  • Darocur a photoinitiator
  • PNIPAM microgels Downstream of the capillary inlet, PNIPAM microgels, which had NH 2 functionality on the surface, were phase-separated from the aqueous PAA phase.
  • the addition of PAA caused the PNIPAM microgels to aggregate due, e.g., to electrostatic interactions.
  • the aggregation process was accelerated by heating the microgels from 20 0 C to about 65 0 C.
  • FIGS. 1A-1C A schematic of this process is shown in FIGS. 1A-1C.
  • the aqueous component formed a distinct phase that appeared to be substantially free of PNIPAM microgels. Downstream of the phase-separation step, the emulsion was exposed to UV radiation, polymerizing the bubbles to form solid articles. The solid particles were then washed with isopropanol to remove oil and were then redispersed in water.
  • the chemical composition of these microspheres was such that one phase was relatively hydrophilic whereas the other one was relatively hydrophobic at high tempereatures (> 35 0 C) and relatively hydrophilic at low temperatures.
  • the particles can be used, for example, as thermosensitive surfactants.
  • the particles can be functionalized in different ways for different applications. For example, in this example cationic PNIPAM microgels (determined by zeta potential measurements) were made. When anionic magnetic particles are added to these microgels, the particles were trapped in the PNIPAM phase, as shown schematically in FIG. 5. Thus, magnetically anisotropic particles can be made for various applications, such as for use in magnetically controlled displays.
  • the relative volumes of the separated PNIPAM phase and the PAA phase were controlled by modifying a variety of process parameters. As shown in FIG. 2A, phase separation occurred at high temperatures. If the droplets ware allowed to cool in water, the PNIPAM phase expanded, incorporating water. Thus, by simply controlling the time interval between the phase separation stage and the UV irradiation, the relative volumes of the two phases was controlled. As illustrated in FIG. 5, the fraction of the final article comprising PNIPAM decreased as the time between the phase separation step and the polymerization step was increased. Additionally, the fraction of the final article comprising PNIPAM increased as the temperature of the emulsion during polymerization was increased. Also, as illustrated in FIG. 6B, increasing the concentration of acrylamide in the aqueous phase led to a decrease in the fraction of the final article comprising PNIPAM.
  • EXAMPLE 4 In this example, a versatile and robust technique to fabricate Janus particles with a novel, highly anisotropic, and finely tunable internal architecture is described. Microparticles with one side composed of a hydrogel and the other side composed predominantly of aggregated colloidal nanoparticles have been generated. The creation of Janus particles with such a unique internal morphology was facilitated by the induced phase separation of colloidal nanoparticles in droplets. By using microfluidic devices, this technique was used to make extremely monodisperse particles; moreover, this technique could also be combined with bulk emulsification methods, such as membrane emulsification, to produce Janus particles in large quantities for more commercially viable applications.
  • bulk emulsification methods such as membrane emulsification
  • the technique was demonstrated by forming Janus particles with polyacrylamide (PAAm) as the hydrogel and poly(N-isopropylacrylamide), PNIPAm, microgels as the nanoparticles.
  • PAAm polyacrylamide
  • PNIPAm poly(N-isopropylacrylamide), PNIPAm
  • the thermosensitive nature of the PNIPAm microgels offered a means of control for precisely tuning the relative volumes of the two phases.
  • the functional dichotomy of the Janus particles was further enhanced by embedding different functional materials selectively into the two sides of the particles as illuistrated by the incorporation of magnetic nanoparticles in the microgel-rich phase of the particles.
  • the process began with an aqueous suspension of ⁇ 500-nm-diameter PNIPAm microgels prepared by precipitation polymerization of N-isopropylacrylamide, NIP Am, monomer. 5 mol % allylamine along with the NIPAm monomer were copolymerized to incorporate reactive amine groups into and onto the microgel particles. The cationic nature of the microgels was confirmed by measuring the electrophoretic mobility of the particles which was found to be 0.9 x 10 '8 m 2 v '1 s "1 .
  • 10 wt% acrylamide was also dissolved in the microgel suspension along with a crosslinker (methylene-bis-acrylamide) and a photoinitiator.
  • This aqueous mixture was emulsified in an oil and heated at 65 0 C in an oven.
  • PNIPAm is a thermosensitive polymer that exhibits a phase transition at -32 °C; the microgels were hydrophobic above this transition temperature and hydrophilic below this temperature.
  • the polydispersity of the Janus particles was set by that of the droplets.
  • monodisperse droplets made using microfiuidic techniques should be used as templates.
  • Drop formation in microfiuidic devices results from a balance of the interfacial tension between the two phases and the shear exerted by the continuous phase on the dispersed phase. Since, the interfacial tension between the two fluids was constant and the shear rate could be precisely adjusted in these devices, droplets with less than 1% polydispersity could be efficiently made.
  • the fabrication of monodisperse Janus particles using a capillary based microfiuidic device was demonstrated.
  • the microfiuidic device was composed of coaxially aligned glass microcapillaries.
  • the outer capillary had a square cross-section and the inner capillary had a round cross-section.
  • the coaxial alignment was achieved by matching the outer dimensions of the round capillary with the inner dimensions of the square capillary.
  • the round capillary Prior to its placement within the square capillary, the round capillary was heated and pulled using a pipette puller to create a gradual taper that culminated in a much finer circular orifice.
  • the square capillary served as a flow channel for the two individual fluid streams while the circular capillary served as a collection tube for the emulsion.
  • a schematic representation of the device and a camera image of the actual device are included in FIGS. 18A-18B.
  • the surfactant-containing silicon oil flowed from one end of the square capillary and focused the monomer-containing aqueous phase flowing from the opposite end into the orifice of the collection tube.
  • the aqueous phase broke into monodisperse droplets upon entering the collection tube to form an emulsion of monodisperse droplets as shown in FIG. 13 A.
  • the emulsion was heated at 65 °C in an oven, which caused the microgels to shrink and compact on one side of the droplets, thus forming monodisperse Janus droplets (FIG. 13B).
  • Monodisperse Janus gel microparticles were formed when the acrylamide was polymerized by exposing the phase separated droplets to UV radiation.
  • FIG. 13C A fluorescent microscope image of the Janus particles is presented in FIG. 13C.
  • the PNIPAm microgels were tagged with rhodamine B to enhance visual contrast between the two phases. Since, the phase separation process occurred downstream of the microfluidics process, the problems associated with the convective mixing of the monomers, often encountered during the co-flow microfluidic techniques for making Janus particles, were eliminated. This technique was not just limited to the fabrication of spherical Janus particles but could also be extended to other shapes. The versatile applicability of this technique was demonstrated by forming a Janus structure in bulk by separating the two hydrogel phases in a glass vial (FIGS. 2C- 2E).
  • the microstructure and phase boundaries of these particles were further probed using a scanning electron microscope (SEM).
  • SEM scanning electron microscope
  • a larger sized Janus particle ( ⁇ 2 mm diameter) was used for this purpose to visually allow suitable orientation of the particle on the SEM specimen stub.
  • the images revealed a rougher surface for the PNIPAm phase in contrast to a relatively smooth surface for the PAAm phase (FIG. 14A).
  • a high magnification micrograph of the PNIPAm phase revealed a raspberry-like structure formed by the aggregation of the PNIPAm microgels (FIG. 14B).
  • the surfaces of both sides revealed wrinkles and stretch marks caused by the dehydration of the hydrogels during sample preparation for electron microscopy.
  • micrographs also revealed a somewhat continuous phase surrounding the PNIPAm microgels, suggesting that not all of the acrylamide was pushed to the opposite side of the drop but some of it was trapped and subsequently polymerized between the microgels. Not wishing to be bound by any theory, this may explain why the volume of the microgel-aggregate did not change with temperature once the phase-separated droplets were UV-irradiated.
  • thermosensitive nature of the PNIPAm microgels could be effectively exploited to adjust the relative volumes of the two phases of these Janus particles.
  • the phase-separated Janus droplets were cooled from 65 0 C to below the phase transition temperature of PNIPAm, the microgels became hydrophilic and began to absorb water from the other side of the drop.
  • the internal morphology of the Janus droplets evolved dynamically during the cooling process.
  • the PNIPAm phase compacted on one side of the drops swelled and occupied an increasingly larger volume of the droplet with time, as shown in FIGS. 15A-15B.
  • the relative volumes of the two phases could be effectively tuned.
  • This range of phase ratios could be further expanded by varying the concentration of the microgels in the aqueous mixture.
  • the size ratios of the two phases could also be adjusted by varying the crosslinker concentration of the PNIPAm microgels. Microgels with a lower crosslinker concentration exhibited a greater equilibrium size change compared to those with a higher crosslinker concentration. Hence, the use of PNIPAm microgels with a lower crosslinker concentration resulted in Janus particles with a wider range of phase ratios as compared to those made using microgels with a higher crosslinker concentration.
  • magnetically anisotropic particles were made by embedding magnetic nanoparticles only in the PNIPAm-rich side of the Janus particles.
  • Anionic magnetic beads were added to the aqueous mixture of the PNIPAm microgels and other monomers. Since the microgel particles were cationic, the magnetic beads covalently bound to the surface of the microgels, and were thus trapped only in the PNIPAm phase of the Janus particles, as shown in FIG. 16.
  • Such magnetically anisotropic particles could be used to make magnetically actuated displays or other applications that require directional orientation or transportation of particles.
  • Cationic materials repelled by the cationic PNIPAm microgels could also be successfully embedded into the PAAm gel of the Janus particles.
  • this example describes the fabrication of spherical Janus microparticles, the concept could be extended to generate Janus structures of various shapes.
  • Microgel Synthesis The PNIPAm microgels were synthesized by precipitation polymerization. NIPAm monomer (4g, 99% purity, Acros) was dissolved along with N, N'- methylene bisacrylamide (0.16g, 99.5% purity, Fluka) and allyl amine (0.14 ml, Sigma- Aldrich) in deionized water (150 ml). The solution was filtered with a 1 -micron filter to remove any particulate impurities and then transferred to a round bottom flask (250 ml) fitted with a stirrer, glass thermometer, condenser, and a nitrogen purge line. The solution was heated to 70 0 C and allowed to equilibrate for 5 minutes under nitrogen.
  • microgel particle size was determined using dynamic light scattering (ALV 5000, 532 nm laser, 90° scattering angle) and fluorescence optical microscopy (Leica TCS-SP5 scanning confocal microscope). A fluorescent micrograph of the synthesized microgels is shown in FIG. 17.
  • Microfluidics A detailed description of the fabrication technique of glass capillary based microfluidic devices has been presented in previous publications. A schematic and an image of an actual capillary based microfluidic device with a flow focusing geometry used for making single emulsions are included in FIGS. 18A-18B.
  • the aqueous phase for microfluidic emulsification was prepared by dissolving PAAc (2xlO "3 wt%, 1.25 xlO 6 g/mol, Carbopol 941, Noveon), acrylamide (10 wt%, 99 wt% purity, Sigma-aldrich), N, N'- methylene bisacrylamide (1 wt%, 99.5% purity, Fluka), and a photoinitiator (2xlO '3 wt%, Darocur 1173) in the microgel suspension.
  • the continuous phase was poly(dimethylsiloxane) fluid (500 cSt, Sigma-Aldrich) containing 0.3 wt% DC547 for emulsion stabilization and the photoinitiator (2x10 '3 wt%, Darocur 1173).
  • the addition of the photoinitiator to the oil phase helped prevent the diffusion of the photoinitiator, which is soluble in both water and oil, out of the drops into the continuous phase.
  • the fluids were pumped into the microfluidic device using syringe pumps (Harvard PHD 2000 series). The flow rates for the continuous and the dispersed fluids were set at 3000 and 500 microliter/hr, respectively.
  • the collected emulsion was heated in an oven at 65 0 C for 45 minutes and was then placed under a UV lamp (Rad-Free, Schleicher & Schuell, 365 nm wavelength).
  • the solidified Janus particles were removed from the silicon oil and repeatedly flushed with isopropanol to remove any adsorbed oil. The particles were then washed and stored under water.
  • the microfluidics process was monitored using an inverted optical microscope (DM-IRB, Leica) fitted with a fast camera (Phantom V5, Vision Research). Characterization: The images for the phase-separated droplets and the Janus particles were taken using an inverted optical microscope fitted with an EMCCD camera (Rolera MGi, Qlmaging).
  • Magnetically anisotropic particles were fabricated by dissolving a ferro-fluid (EMG 708, Ferrotec) in the aqueous mixture. For ease of visualization, large Janus particles made using 25- microliter droplets as templates were used for this purpose.
  • a reference to "A and/or B", when used in conjunction with open-ended language such as “comprising” can refer, in one embodiment, to A only (optionally including elements other than B); in another embodiment, to B only (optionally including elements other than A); in yet another embodiment, to both A and B (optionally including other elements); etc.
  • At least one of A and B can refer, in one embodiment, to at least one, optionally including more than one, A, with no B present (and optionally including elements other than B); in another embodiment, to at least one, optionally including more than one, B, with no A present (and optionally including elements other than A); in yet another embodiment, to at least one, optionally including more than one, A, and at least one, optionally including more than one, B (and optionally including other elements); etc.

Abstract

La présente invention concerne d'une manière générale des entités polyphasiques, qui peuvent comprendre une ou plusieurs phases contenant des particules. Les particules peuvent être agglomérées dans certains cas. Dans des modes de réalisation, l'entité polyphasique contient une ou plusieurs phases et/ou régions, qui peuvent chacune indépendamment être un solide ou un liquide. Par exemple, une entité polyphasique peut contenir une phase solide et une phase liquide, une première phase solide et une seconde phase solide, une première phase liquide et une seconde phase liquide, etc., et les phases peuvent être présentes à l'intérieur d'une ou de plusieurs phases à l'intérieur de l'entité. Sous certains aspects de l'invention, les caractères hydrophobes/hydrophiles d'une ou de plusieurs phases de l'entité polyphasique sont sensibles à la température, au pH et/ou à une substance à analyser, etc. Encore d'autres aspects de l'invention concernent d'une manière générale des systèmes et des procédés de fabrication et d'utilisation de telles entités polyphasiques, sur des kits mettant en jeu de telles entités, ou autres.
PCT/US2008/012384 2007-11-02 2008-10-31 Systèmes et procédés pour créer des entités polyphasiques, comprenant des particules et/ou des fluides WO2009061372A1 (fr)

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Cited By (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8465707B2 (en) 2010-07-22 2013-06-18 Gencell Biosystems Ltd. Composite liquid cells
US8622987B2 (en) 2008-06-04 2014-01-07 The University Of Chicago Chemistrode, a plug-based microfluidic device and method for stimulation and sampling with high temporal, spatial, and chemical resolution
US20140235808A1 (en) * 2013-02-19 2014-08-21 Postech Academy-Industry Foundation Microdroplet or microparticle with janus or core-shell internal morphology fabricated from n-isopropylacrylamide
US9039273B2 (en) 2005-03-04 2015-05-26 President And Fellows Of Harvard College Method and apparatus for forming multiple emulsions
US9238206B2 (en) 2011-05-23 2016-01-19 President And Fellows Of Harvard College Control of emulsions, including multiple emulsions
WO2016070016A1 (fr) * 2014-10-31 2016-05-06 Massachusetts Institute Of Technology Compositions et méthodes de formation d'émulsions
US9388465B2 (en) 2013-02-08 2016-07-12 10X Genomics, Inc. Polynucleotide barcode generation
US9410201B2 (en) 2012-12-14 2016-08-09 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9689024B2 (en) 2012-08-14 2017-06-27 10X Genomics, Inc. Methods for droplet-based sample preparation
US9694361B2 (en) 2014-04-10 2017-07-04 10X Genomics, Inc. Fluidic devices, systems, and methods for encapsulating and partitioning reagents, and applications of same
US9701998B2 (en) 2012-12-14 2017-07-11 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9777269B2 (en) 2012-01-25 2017-10-03 Gencell Biosystems Ltd. Biomolecule isolation
US9776182B2 (en) 2012-11-27 2017-10-03 Gencell Biosystems Ltd. Handling liquid samples
US9824068B2 (en) 2013-12-16 2017-11-21 10X Genomics, Inc. Methods and apparatus for sorting data
US9951386B2 (en) 2014-06-26 2018-04-24 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9975122B2 (en) 2014-11-05 2018-05-22 10X Genomics, Inc. Instrument systems for integrated sample processing
US10005058B2 (en) 2014-10-31 2018-06-26 Massachusetts Institute Of Technology Compositions and methods for arranging colloid phases
US10011872B1 (en) 2016-12-22 2018-07-03 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10060913B2 (en) 2016-09-19 2018-08-28 Massachusetts Institute Of Technology Systems including janus droplets capable of binding an analyte and changing orientation to provide a detectable change
EP3237556A4 (fr) * 2014-12-24 2018-08-29 National Research Council of Canada Microparticules et appareil de production d'encre intelligente
US10195571B2 (en) 2011-07-06 2019-02-05 President And Fellows Of Harvard College Multiple emulsions and techniques for the formation of multiple emulsions
US10221442B2 (en) 2012-08-14 2019-03-05 10X Genomics, Inc. Compositions and methods for sample processing
US10221436B2 (en) 2015-01-12 2019-03-05 10X Genomics, Inc. Processes and systems for preparation of nucleic acid sequencing libraries and libraries prepared using same
US10273541B2 (en) 2012-08-14 2019-04-30 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10287623B2 (en) 2014-10-29 2019-05-14 10X Genomics, Inc. Methods and compositions for targeted nucleic acid sequencing
US10323279B2 (en) 2012-08-14 2019-06-18 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10384187B2 (en) 2014-02-10 2019-08-20 Gencell Biosystems Ltd Composite liquid cell (CLC) mediated nucleic acid library preparation device, and methods for using the same
US10395758B2 (en) 2013-08-30 2019-08-27 10X Genomics, Inc. Sequencing methods
US10400235B2 (en) 2017-05-26 2019-09-03 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
US10400280B2 (en) 2012-08-14 2019-09-03 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10428326B2 (en) 2017-01-30 2019-10-01 10X Genomics, Inc. Methods and systems for droplet-based single cell barcoding
US10533221B2 (en) 2012-12-14 2020-01-14 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10550429B2 (en) 2016-12-22 2020-02-04 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10650912B2 (en) 2015-01-13 2020-05-12 10X Genomics, Inc. Systems and methods for visualizing structural variation and phasing information
US10697000B2 (en) 2015-02-24 2020-06-30 10X Genomics, Inc. Partition processing methods and systems
US10745742B2 (en) 2017-11-15 2020-08-18 10X Genomics, Inc. Functionalized gel beads
US10752949B2 (en) 2012-08-14 2020-08-25 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10774370B2 (en) 2015-12-04 2020-09-15 10X Genomics, Inc. Methods and compositions for nucleic acid analysis
US10815525B2 (en) 2016-12-22 2020-10-27 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10829815B2 (en) 2017-11-17 2020-11-10 10X Genomics, Inc. Methods and systems for associating physical and genetic properties of biological particles
US10839939B2 (en) 2014-06-26 2020-11-17 10X Genomics, Inc. Processes and systems for nucleic acid sequence assembly
US10854315B2 (en) 2015-02-09 2020-12-01 10X Genomics, Inc. Systems and methods for determining structural variation and phasing using variant call data
US10874997B2 (en) 2009-09-02 2020-12-29 President And Fellows Of Harvard College Multiple emulsions created using jetting and other techniques
US11081208B2 (en) 2016-02-11 2021-08-03 10X Genomics, Inc. Systems, methods, and media for de novo assembly of whole genome sequence data
US11084036B2 (en) 2016-05-13 2021-08-10 10X Genomics, Inc. Microfluidic systems and methods of use
US11119098B2 (en) 2014-10-31 2021-09-14 Massachusetts Institute Of Technology Systems including Janus droplets
US11155881B2 (en) 2018-04-06 2021-10-26 10X Genomics, Inc. Systems and methods for quality control in single cell processing
US11274343B2 (en) 2015-02-24 2022-03-15 10X Genomics, Inc. Methods and compositions for targeted nucleic acid sequence coverage
US11591637B2 (en) 2012-08-14 2023-02-28 10X Genomics, Inc. Compositions and methods for sample processing
US11629344B2 (en) 2014-06-26 2023-04-18 10X Genomics, Inc. Methods and systems for processing polynucleotides
US11773389B2 (en) 2017-05-26 2023-10-03 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
US11898206B2 (en) 2017-05-19 2024-02-13 10X Genomics, Inc. Systems and methods for clonotype screening

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005072334A2 (fr) * 2004-01-23 2005-08-11 Arizona Board Of Regents For And On Behalf Of Arizona State University Hydrogels photosensibles
WO2006096571A2 (fr) * 2005-03-04 2006-09-14 President And Fellows Of Harvard College Procede et dispositif permettant de former des emulsions multiples

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005072334A2 (fr) * 2004-01-23 2005-08-11 Arizona Board Of Regents For And On Behalf Of Arizona State University Hydrogels photosensibles
WO2006096571A2 (fr) * 2005-03-04 2006-09-14 President And Fellows Of Harvard College Procede et dispositif permettant de former des emulsions multiples

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
A. WEITZ ET AL.: "Monodisperse Thermoresponsive Microgels with Tunable Volume-Phase Transition Kinetics", ADV. FUNCT. MATER., vol. 17, 31 October 2007 (2007-10-31), pages 3499 - 3504, XP002519143 *
M. LATTUADA ET AL.: "Preparation and controlled Self-Assembly of Janus Magnetic Nanoparticles", JACS, vol. 129, no. 42, 2 October 2007 (2007-10-02), pages 12878 - 12889, XP002518539 *
NAKASHIMA K ET AL: "Aggregation of water-soluble block copolymers in aqueous solutions: Recent trends", ADVANCES IN COLLOID AND INTERFACE SCIENCE, ELSEVIER, vol. 123-126, 16 November 2006 (2006-11-16), pages 75 - 96, XP025061740, ISSN: 0001-8686, [retrieved on 20061116] *
P. KUJAWA ET AL.: "Temperature-Sensitive Properties of Poly(n-isopropylacrylamide) Mesoglobules formed in dilute Aqueous Solutions Heated above Their Demixing Point", MACROMOLECULES, vol. 39, no. 22, 10 October 2006 (2006-10-10), pages 7686 - 7693, XP002518540 *
RODRIGUEZ-HERNANDEZ ET AL: "Toward 'smart' nano-objects by self-assembly of block copolymers in solution", PROGRESS IN POLYMER SCIENCE, PERGAMON PRESS, OXFORD, GB, vol. 30, no. 7, 1 July 2005 (2005-07-01), pages 691 - 724, XP005012873, ISSN: 0079-6700 *

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US10125389B2 (en) 2010-07-22 2018-11-13 Gencell Biosystems Limited Composite liquid cells
US9080208B2 (en) 2010-07-22 2015-07-14 Gencell Biosystems Ltd. Composite liquid cells
US8465707B2 (en) 2010-07-22 2013-06-18 Gencell Biosystems Ltd. Composite liquid cells
US9493816B2 (en) 2010-07-22 2016-11-15 GenCell Biosytems Ltd. Composite liquid cells
US9238206B2 (en) 2011-05-23 2016-01-19 President And Fellows Of Harvard College Control of emulsions, including multiple emulsions
US9573099B2 (en) 2011-05-23 2017-02-21 President And Fellows Of Harvard College Control of emulsions, including multiple emulsions
US10195571B2 (en) 2011-07-06 2019-02-05 President And Fellows Of Harvard College Multiple emulsions and techniques for the formation of multiple emulsions
US10081808B2 (en) 2012-01-25 2018-09-25 Gencell Biosystems Ltd Biomolecule isolation
US9777269B2 (en) 2012-01-25 2017-10-03 Gencell Biosystems Ltd. Biomolecule isolation
US11035002B2 (en) 2012-08-14 2021-06-15 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10221442B2 (en) 2012-08-14 2019-03-05 10X Genomics, Inc. Compositions and methods for sample processing
US9695468B2 (en) 2012-08-14 2017-07-04 10X Genomics, Inc. Methods for droplet-based sample preparation
US10450607B2 (en) 2012-08-14 2019-10-22 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9689024B2 (en) 2012-08-14 2017-06-27 10X Genomics, Inc. Methods for droplet-based sample preparation
US10669583B2 (en) 2012-08-14 2020-06-02 10X Genomics, Inc. Method and systems for processing polynucleotides
US10273541B2 (en) 2012-08-14 2019-04-30 10X Genomics, Inc. Methods and systems for processing polynucleotides
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US10400280B2 (en) 2012-08-14 2019-09-03 10X Genomics, Inc. Methods and systems for processing polynucleotides
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US11591637B2 (en) 2012-08-14 2023-02-28 10X Genomics, Inc. Compositions and methods for sample processing
US11078522B2 (en) 2012-08-14 2021-08-03 10X Genomics, Inc. Capsule array devices and methods of use
US10053723B2 (en) 2012-08-14 2018-08-21 10X Genomics, Inc. Capsule array devices and methods of use
US10597718B2 (en) 2012-08-14 2020-03-24 10X Genomics, Inc. Methods and systems for sample processing polynucleotides
US11021749B2 (en) 2012-08-14 2021-06-01 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10584381B2 (en) 2012-08-14 2020-03-10 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9776182B2 (en) 2012-11-27 2017-10-03 Gencell Biosystems Ltd. Handling liquid samples
US10252261B2 (en) 2012-11-27 2019-04-09 Gencell Biosystems Ltd. Handling liquid samples
US10253364B2 (en) 2012-12-14 2019-04-09 10X Genomics, Inc. Method and systems for processing polynucleotides
US9410201B2 (en) 2012-12-14 2016-08-09 10X Genomics, Inc. Methods and systems for processing polynucleotides
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US10612090B2 (en) 2012-12-14 2020-04-07 10X Genomics, Inc. Methods and systems for processing polynucleotides
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US10227648B2 (en) 2012-12-14 2019-03-12 10X Genomics, Inc. Methods and systems for processing polynucleotides
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US10676789B2 (en) 2012-12-14 2020-06-09 10X Genomics, Inc. Methods and systems for processing polynucleotides
US9388465B2 (en) 2013-02-08 2016-07-12 10X Genomics, Inc. Polynucleotide barcode generation
US10150964B2 (en) 2013-02-08 2018-12-11 10X Genomics, Inc. Partitioning and processing of analytes and other species
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US11193121B2 (en) 2013-02-08 2021-12-07 10X Genomics, Inc. Partitioning and processing of analytes and other species
US10150963B2 (en) 2013-02-08 2018-12-11 10X Genomics, Inc. Partitioning and processing of analytes and other species
US20140235808A1 (en) * 2013-02-19 2014-08-21 Postech Academy-Industry Foundation Microdroplet or microparticle with janus or core-shell internal morphology fabricated from n-isopropylacrylamide
KR101494508B1 (ko) * 2013-02-19 2015-02-23 포항공과대학교 산학협력단 나이팜 단일성분으로 이루어진 야누스 또는 코어-쉘 형태의 미세액적 또는 미세입자
US9718904B2 (en) 2013-02-19 2017-08-01 Postech Acadmey-Industry Foundation Microdroplet or microparticle with Janus or core-shell internal morphology fabricated from N-isopropylacrylamide
US10395758B2 (en) 2013-08-30 2019-08-27 10X Genomics, Inc. Sequencing methods
US9824068B2 (en) 2013-12-16 2017-11-21 10X Genomics, Inc. Methods and apparatus for sorting data
US10384187B2 (en) 2014-02-10 2019-08-20 Gencell Biosystems Ltd Composite liquid cell (CLC) mediated nucleic acid library preparation device, and methods for using the same
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US10137449B2 (en) 2014-04-10 2018-11-27 10X Genomics, Inc. Fluidic devices, systems, and methods for encapsulating and partitioning reagents, and applications of same
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US10457986B2 (en) 2014-06-26 2019-10-29 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10030267B2 (en) 2014-06-26 2018-07-24 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10480028B2 (en) 2014-06-26 2019-11-19 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10839939B2 (en) 2014-06-26 2020-11-17 10X Genomics, Inc. Processes and systems for nucleic acid sequence assembly
US11713457B2 (en) 2014-06-26 2023-08-01 10X Genomics, Inc. Methods and systems for processing polynucleotides
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US10344329B2 (en) 2014-06-26 2019-07-09 10X Genomics, Inc. Methods and systems for processing polynucleotides
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US9951386B2 (en) 2014-06-26 2018-04-24 10X Genomics, Inc. Methods and systems for processing polynucleotides
US11133084B2 (en) 2014-06-26 2021-09-28 10X Genomics, Inc. Systems and methods for nucleic acid sequence assembly
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US10760124B2 (en) 2014-06-26 2020-09-01 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10287623B2 (en) 2014-10-29 2019-05-14 10X Genomics, Inc. Methods and compositions for targeted nucleic acid sequencing
US11739368B2 (en) 2014-10-29 2023-08-29 10X Genomics, Inc. Methods and compositions for targeted nucleic acid sequencing
US11229892B2 (en) 2014-10-31 2022-01-25 Massachusetts Institute Of Technology Compositions and methods for forming emulsions
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US10245587B2 (en) 2014-11-05 2019-04-02 10X Genomics, Inc. Instrument systems for integrated sample processing
US11135584B2 (en) 2014-11-05 2021-10-05 10X Genomics, Inc. Instrument systems for integrated sample processing
US9975122B2 (en) 2014-11-05 2018-05-22 10X Genomics, Inc. Instrument systems for integrated sample processing
EP3237556A4 (fr) * 2014-12-24 2018-08-29 National Research Council of Canada Microparticules et appareil de production d'encre intelligente
US10836918B2 (en) 2014-12-24 2020-11-17 National Research Council Of Canada Microparticles and apparatus for smart ink production
US10221436B2 (en) 2015-01-12 2019-03-05 10X Genomics, Inc. Processes and systems for preparation of nucleic acid sequencing libraries and libraries prepared using same
US10557158B2 (en) 2015-01-12 2020-02-11 10X Genomics, Inc. Processes and systems for preparation of nucleic acid sequencing libraries and libraries prepared using same
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US10650912B2 (en) 2015-01-13 2020-05-12 10X Genomics, Inc. Systems and methods for visualizing structural variation and phasing information
US10854315B2 (en) 2015-02-09 2020-12-01 10X Genomics, Inc. Systems and methods for determining structural variation and phasing using variant call data
US11603554B2 (en) 2015-02-24 2023-03-14 10X Genomics, Inc. Partition processing methods and systems
US10697000B2 (en) 2015-02-24 2020-06-30 10X Genomics, Inc. Partition processing methods and systems
US11274343B2 (en) 2015-02-24 2022-03-15 10X Genomics, Inc. Methods and compositions for targeted nucleic acid sequence coverage
US11473125B2 (en) 2015-12-04 2022-10-18 10X Genomics, Inc. Methods and compositions for nucleic acid analysis
US11873528B2 (en) 2015-12-04 2024-01-16 10X Genomics, Inc. Methods and compositions for nucleic acid analysis
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US11624085B2 (en) 2015-12-04 2023-04-11 10X Genomics, Inc. Methods and compositions for nucleic acid analysis
US11081208B2 (en) 2016-02-11 2021-08-03 10X Genomics, Inc. Systems, methods, and media for de novo assembly of whole genome sequence data
US11084036B2 (en) 2016-05-13 2021-08-10 10X Genomics, Inc. Microfluidic systems and methods of use
US10060913B2 (en) 2016-09-19 2018-08-28 Massachusetts Institute Of Technology Systems including janus droplets capable of binding an analyte and changing orientation to provide a detectable change
US10858702B2 (en) 2016-12-22 2020-12-08 10X Genomics, Inc. Methods and systems for processing polynucleotides
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US11180805B2 (en) 2016-12-22 2021-11-23 10X Genomics, Inc Methods and systems for processing polynucleotides
US10815525B2 (en) 2016-12-22 2020-10-27 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10793905B2 (en) 2016-12-22 2020-10-06 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10323278B2 (en) 2016-12-22 2019-06-18 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10011872B1 (en) 2016-12-22 2018-07-03 10X Genomics, Inc. Methods and systems for processing polynucleotides
US10480029B2 (en) 2016-12-22 2019-11-19 10X Genomics, Inc. Methods and systems for processing polynucleotides
US11193122B2 (en) 2017-01-30 2021-12-07 10X Genomics, Inc. Methods and systems for droplet-based single cell barcoding
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US10844372B2 (en) 2017-05-26 2020-11-24 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
US10400235B2 (en) 2017-05-26 2019-09-03 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
US11155810B2 (en) 2017-05-26 2021-10-26 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
US11773389B2 (en) 2017-05-26 2023-10-03 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
US11198866B2 (en) 2017-05-26 2021-12-14 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
US10927370B2 (en) 2017-05-26 2021-02-23 10X Genomics, Inc. Single cell analysis of transposase accessible chromatin
US10876147B2 (en) 2017-11-15 2020-12-29 10X Genomics, Inc. Functionalized gel beads
US10745742B2 (en) 2017-11-15 2020-08-18 10X Genomics, Inc. Functionalized gel beads
US11884962B2 (en) 2017-11-15 2024-01-30 10X Genomics, Inc. Functionalized gel beads
US10829815B2 (en) 2017-11-17 2020-11-10 10X Genomics, Inc. Methods and systems for associating physical and genetic properties of biological particles
US11155881B2 (en) 2018-04-06 2021-10-26 10X Genomics, Inc. Systems and methods for quality control in single cell processing

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