US20160144329A1 - Systems for Encapsulation of Actives within Droplets and other Compartments - Google Patents

Systems for Encapsulation of Actives within Droplets and other Compartments Download PDF

Info

Publication number: US20160144329A1
Authority: US; United States
Prior art keywords: fluid; microparticles; less; entities; agent
Prior art date: 2014-11-24
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.): Abandoned

Application number

US14/945,479

Other languages

English (en)

Inventor

John Christopher Wesner

Marco Caggioni

Taotao Zhu

David A Weitz

Alireza Abbaspourrad

Chang-Hyung CHOI

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Procter and Gamble Co

Harvard University

Original Assignee

Procter and Gamble Co

Harvard University

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2014-11-24

Filing date

2015-11-19

Publication date

2016-05-26

2015-11-19 Application filed by Procter and Gamble Co, Harvard University filed Critical Procter and Gamble Co

2015-11-19 Priority to US14/945,479 priority Critical patent/US20160144329A1/en

2016-05-26 Publication of US20160144329A1 publication Critical patent/US20160144329A1/en

2016-06-14 Assigned to THE PROCTER & GAMBLE COMPANY, PRESIDENT AND FELLOWS OF HARWARD COLLEGE reassignment THE PROCTER & GAMBLE COMPANY ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: CHOI, CHANG-HYUNG, ABBASPOURRAD, Alireza, Weitz, David A, CAGGIONI, MARCO, WESNER, JOHN CHRISTOPHER, ZHU, TAOTAO

Status Abandoned legal-status Critical Current

Images

Classifications

- 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
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
- A61K8/11—Encapsulated compositions
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/81—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions involving only carbon-to-carbon unsaturated bonds
- A61K8/8129—Compositions of homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical; Compositions of hydrolysed polymers or esters of unsaturated alcohols with saturated carboxylic acids; Compositions of derivatives of such polymers, e.g. polyvinylmethylether
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/86—Polyethers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5089—Processes
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q13/00—Formulations or additives for perfume preparations
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/40—Mixing liquids with liquids; Emulsifying
- B01F23/41—Emulsifying
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/40—Mixing liquids with liquids; Emulsifying
- B01F23/41—Emulsifying
- B01F23/414—Emulsifying characterised by the internal structure of the emulsion
- B01F23/4144—Multiple emulsions, in particular double emulsions, e.g. water in oil in water; Three-phase emulsions
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/20—Jet mixers, i.e. mixers using high-speed fluid streams
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F25/30—Injector mixers
- B01F25/31—Injector mixers in conduits or tubes through which the main component flows
- B01F25/313—Injector mixers in conduits or tubes through which the main component flows wherein additional components are introduced in the centre of the conduit
- 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
- B01F33/301—Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions
- B01F33/3011—Micromixers using specific means for arranging the streams to be mixed, e.g. channel geometries or dispositions using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
- 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
- B01F33/3022—Micromixers the materials to be mixed flowing in the form of droplets the components being formed by independent droplets which are alternated, the mixing of the components being achieved by diffusion between 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
- B01F33/80—Mixing plants; Combinations of mixers
- B01F33/81—Combinations of similar mixers, e.g. with rotary stirring devices in two or more receptacles
- B01F33/813—Combinations of similar mixers, e.g. with rotary stirring devices in two or more receptacles mixing simultaneously in two or more mixing receptacles
- 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
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
- 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
- C09K15/00—Anti-oxidant compositions; Compositions inhibiting chemical change
- C09K15/04—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds
- C09K15/06—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing oxygen
- C09K15/08—Anti-oxidant compositions; Compositions inhibiting chemical change containing organic compounds containing oxygen containing a phenol or quinone moiety
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11B—PRODUCING, e.g. BY PRESSING RAW MATERIALS OR BY EXTRACTION FROM WASTE MATERIALS, REFINING OR PRESERVING FATS, FATTY SUBSTANCES, e.g. LANOLIN, FATTY OILS OR WAXES; ESSENTIAL OILS; PERFUMES
- C11B9/00—Essential oils; Perfumes
- C11B9/0042—Essential oils; Perfumes compounds containing condensed hydrocarbon rings
- C11B9/0046—Essential oils; Perfumes compounds containing condensed hydrocarbon rings containing only two condensed rings
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/41—Particular ingredients further characterized by their size
- A61K2800/412—Microsized, i.e. having sizes between 0.1 and 100 microns
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F25/00—Flow mixers; Mixers for falling materials, e.g. solid particles
- B01F2025/91—Direction of flow or arrangement of feed and discharge openings
- B01F2025/918—Counter current flow, i.e. flows moving in opposite direction and colliding
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01F—MIXING, e.g. DISSOLVING, EMULSIFYING OR DISPERSING
- B01F23/00—Mixing according to the phases to be mixed, e.g. dispersing or emulsifying
- B01F23/40—Mixing liquids with liquids; Emulsifying
- B01F23/41—Emulsifying
- B01F23/414—Emulsifying characterised by the internal structure of the emulsion
- B01F23/4143—Microemulsions
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2984—Microcapsule with fluid core [includes liposome]

Definitions

the present invention generally relates to microparticles and, in particular, to systems and methods for encapsulation within microparticles.
Microparticles such as microcapsules have great potential for applications involving encapsulation, delivery, and release of agents in fields such as agriculture, health care, cosmetics and detergents, construction chemicals, and food and beverages.
a variety of physical and chemical methods including spray-drying, coextrusion, interfacial polymerization, and complex coacervation, have been used for high-throughput preparation of microparticles.
a variety of agents have been encapsulated into emulsions, which are then solidified to form solid microparticles or other types of particles, for instance, by interfacial polycondensation, freezing, or polymerization.
improvements in particle technologies are still needed.
the present invention generally relates to microparticles and, in particular, to systems and methods for encapsulation within microparticles.
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 present invention is generally directed to a method.
the method is a method of release of agent from a particle, such as a microparticle.
the method includes an act of exposing, to an environment, a plurality of microparticles comprising a shell and a fluid within the shell, the fluid comprising a plurality of entities containing an agent, and causing release of at least about 50 wt % of the agent from the plurality of microcapsules without disruption of the shell.
the present invention in another aspect, is generally directed to a composition.
the composition comprises a plurality of microparticles comprising a shell and a fluid within the shell, the fluid comprising a plurality of entities containing an agent, where at least 50 wt % of the agent is releasable from the microparticles without disruption of the shell.
the composition comprises a plurality of microparticles comprising a shell and a fluid within the shell, the fluid comprising a plurality of entities containing an agent, where the plurality of entities within the shell has a volume of at least 50% of the volume of the shell.
a composition in one aspect, includes a plurality of microparticles.
Each microparticle includes a single core which contains a liquid emulsion having a dispersed phase and a continuous phase; and a shell surrounding the single core.
the shell has a mean wall thickness of between about 0.1 ⁇ m, and about 10 ⁇ m.
a composition in one aspect, includes a plurality of microparticles.
Each microparticle includes a single core which contains a liquid emulsion having a dispersed phase and a continuous phase; and a shell surrounding the single core.
the shell has a mean wall thickness of between about 0.1 ⁇ m, and about 10 ⁇ m.
the core comprises an aqueous phase, an oil phase, and a surfactant.
the present invention encompasses methods of making one or more of the embodiments described herein, for example, microfluidic droplets encapsulating entities.
the method is directed to the production of microparticles and includes the steps of: providing a first liquid to a system of microfluidic devices, introducing a stream of the first liquid into a stream of a second liquid, introducing a stream of a third liquid which surrounds the second liquid, and forming droplets within the third liquid.
the first liquid includes an emulsion having a dispersed phase and a continuous phase as it is introduced into the second liquid.
the continuous phase of the first liquid is substantially immiscible in the second liquid.
the droplets comprise a core including the first liquid and a shell comprised of the second liquid.
an apparatus for producing microparticles includes: a first reservoir containing a first liquid, a second reservoir containing a second liquid, and a third reservoir containing a third liquid.
the first liquid includes an emulsion.
the emulsion includes a dispersed phase and a continuous phase.
the continuous phase of the emulsion is substantially immiscible in the second fluid.
the first reservoir is in fluid communication with the first conduits of a plurality of microfluidic devices.
the first conduits have exits.
the second reservoir in is fluid communication with second conduits.
the second conduits at least partially surround the first conduits.
the third reservoir is in fluid communication with the second conduits.
the apparatus also includes third conduits disposed, at least in part, within the second conduits, downstream of the exits of the first conduits.
the present invention encompasses methods of using one or more of the embodiments described herein, for example, microfluidic droplets encapsulating entities.
FIGS. 1A-1D illustrate methods useful for forming microparticles, in accordance with one embodiment of the invention
FIG. 2 illustrates the production of a particle suspension, in another embodiment of the invention
FIG. 3 illustrates the structure of a microparticle, in yet another embodiment of the invention.
FIG. 4 illustrates a device for producing particle suspensions, in still another embodiment of the invention.
FIG. 5 illustrates data associated with the relative stability of microcapsules having a hydrogel continuous phase and control microcapsules having an aqueous continuous phase.
FIG. 6 provides a schematic illustration of an apparatus according to one embodiment of the invention.
the present invention generally relates to microparticles and, in particular, to systems and methods for encapsulation within microparticles.
the present invention is generally directed to microparticles containing entities therein, where the entities contain an agent that can be released from the microparticles, e.g., via diffusion.
the agent may be released from the microparticles without disruption of the microparticles.
the entities may be, for instance, polymeric particles, hydrogel particles, droplets of fluid, etc.
the entities may be contained within a fluid that is, in turn, encapsulated within the microparticle.
the agent may be released from the entity into the fluid, and then from the fluid through the microparticle.
microparticle release of agent from the microparticle may be controlled, e.g., over relatively long time scales.
Other embodiments of the present invention are generally directed to methods of making such microparticles, methods of using such microparticles, microfluidic devices for making such microparticles, and the like.
a microparticle 10 comprises a shell 15 surrounding a fluid 20 .
the entities may be, for example, polymeric particles, hydrogel particles, droplets of an immiscible fluid, or the like.
the entities may also contain an agent 30 to be released from microparticle 10 .
agent 30 must travel from entities 25 through fluid 20 and shell 15 .
shell 15 may be kept intact or undamaged during the release of agent 30 .
agent 30 may diffuse out of entities 25 , through fluid 20 , and through shell 15 , before being released from microparticle 10 .
the microparticles in certain embodiments, can provide for the controlled rate of release of agent 30 .
the fluid 20 comprises an emulsion comprising a continuous phase and a dispersed phase.
the entities may comprise the dispersed phase of the emulsion.
the continuous phase may constitute an aqueous phase and the dispersed phase may constitute an oil phase.
the fluid may further comprise a surfactant.
the first fluid may comprise a suspo-emulsion comprising a continuous phase and particles suspended in the continuous phase.
Exemplary emulsions may be created by dispersing an oil phase material in an aqueous phase with mechanical agitation.
Exemplary forms of mechanical agitation include: shaking, mixing, agitators, sonication, colloid mills, rotors, rotor-stator, static mixers, flow-through static mixers, homogenizers, high-shear microfluidic collision processors, a Microfluidizer®, vortex mixers, a speed mixer, and a high shear homogenizer.
Exemplary emulsions include an emulsion of 0.1-0.4 wt % Permulen TR-2 surfactant in perfume oil, and an emulsion of ⁇ -pinene in a solution of 2.5% (v/v) PVA and 2% (w/w) Tween 80.
Exemplary continuous phase materials for the first liquid include: water, glycerine, formamide, dimethyl formamide, dimethyl sulfoxide, polyethylene glycol, propylene glycol, and fluorinated oils.
the release profile may be relatively slow, e.g., having a characteristic time of release of hours or days.
the rate of release of agent from the microparticle may not necessarily be controlled by the amount of agent contained within the microparticle; for example, diffusion of the agent through the fluid may be rate-limiting, and the entities may act as a reservoir to contain agent prior to diffusion through the fluid.
the amount and rate of agent released from the particle is usually a function of the amount of agent contained within the particle.
the microparticles may be exposed to an environment to which the agent is to be released.
the agent may be caused to be released from the microparticles via a variety of techniques. The release of agent may occur without disrupting the microparticles, e.g., by damaging the shell of the microparticles to release the agent from within.
the agent may be released by agitating the microparticles.
the microparticles may be exposed to a fluid, such as oil (e.g., a hydrocarbon oil, crude oil, petroleum, etc.), or to water.
the agent may diffuse through the microparticles to be released at the surface of the microparticles into the surrounding environment, e.g., if the microparticles are contained in a fluid, such as an oil or water.
FIG. 4 describes one non-limiting system for producing such microparticles.
a fluid 20 containing entities 25 suspended therein flows through a first channel 30 .
fluid 20 becomes encapsulated within microparticles.
first channel 30 has an exit opening 34 contained within channel 40 .
fluid 45 which will be used to produce the shell of the microparticle, and fluid 50 , which will contain the microparticles.
fluid 45 flows around channel 30 towards exit opening 34 of channel 30 , where it surrounds fluid 20 emerging out of the exit opening. In turn fluid 45 is surrounded by fluid 50 .
Fluids 45 and 50 may be substantially immiscible in certain embodiments.
multiple emulsion droplets may be formed, containing fluid 20 , surrounded by droplets of fluid 45 , contained within continuous fluid 50 .
Fluid 45 may also be hardened or reacted to form a shell surrounding fluid 20 by, for example, exposing the formed droplet to appropriate electromagnetic radiation. See also Int. Pat. Apl. Pub. Nos. WO 2006/096571 or WO 2013/006661, each incorporated herein by reference in its entirety, for other examples.
the microparticles may comprise a plurality of entities therein containing one or more agents. Any suitable entities able to contain an agent and remain as separate entities when contained within a fluid may be used.
the entities may be solid, or fluid in some embodiments.
the entities may be a second fluid that is substantially immiscible within the fluid within the microparticles.
the entities may be substantially prevented from merging or coalescing together using surfactant or other suitable techniques.
the entities are able to remain as discrete or separate entities within the fluid.
the fluid within the microparticles is aqueous (e.g., a “water” phase)
the fluid forming the entities may be a non-aqueous fluid that is substantially immiscible within the aqueous fluid (e.g., an “oil” phase), or vice versa.
the entities may comprise a fluid which is substantially miscible in the shell of the microparticles.
water phase is not limited to only pure water, but may be any fluid miscible in water, and/or the fluid may be water but contain other substances dissolved or suspended therein, etc.
the “oil” phase need not be a hydrocarbon oil, but may be any fluid that is substantially immiscible in water. Accordingly, the terms “oil” and “water” are used as terms of convenience, as is typically expressed by those of ordinary skill in the art.
the entities contained within the microparticles need not be fluid.
the entities may be particles, for example, polymeric particles or hydrogel particles, etc. Any of a wide variety of particles may be used, for example, that can be contained or suspended in a fluid that is to be encapsulated within a microparticle.
the entities may comprise hydrogels such as agarose, polyacrylamide, poly(N-isopropylacrylamide), or the like, or polymers such as polystyrene, polypropylene, polyethylene, polycaprolactone, polyisoprene, poly(lactic acid), polycaprolactone, poly(lactic acid), polyacrylonitrile, polyimide, polyamide, and/or mixtures and/or co-polymers of these and/or other polymers.
the polymeric particles may be formed using microfluidic techniques known to those of ordinary skill in the art, or using other techniques that are not necessarily microfluidic. In some cases, the particles are nanoparticles e.g., having an average diameter of less than 1 micrometer.
any suitable number of entities may be contained within a microparticle. In some embodiments, however, there may be a relatively large number of entities contained within a microparticle, e.g., if the entities are relatively small relative to the size of the microparticles. In some cases, entities with relatively high loading densities may be achieved, as discussed herein, by starting with a fluid having a relatively high loading density of such entities.
the entities may be relatively small in some embodiments.
the entities may have an average diameter of less than about 1 micrometer, less than about 500 nm, less than about 300 nm, less than about 200 nm, less than about 100 nm, less than about 50 nm, less than about 30 nm, less than about 20 nm, or less than about 10 nm, etc.
the entity may be spherical or non-spherical.
the average diameter of a non-spherical entity may be taken as the diameter of a perfect sphere having the same volume as the non-spherical entity.
the entities may have an average diameter that is less than about 30%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 3%, less than about 2%, less than about 1%, less than about 0.5%, less than about 0.3%, less than about 0.2%, less than about 0.1%, or less than about 0.05% of the average diameter of the microparticle containing the entities.
the diameter or volume of the entities may be determined directly, e.g., using optical or electron microscopy, and or estimated, e.g., based on the overall volume of entities contained within the microparticles.
the microparticles may each contain, on average, at least about 100, at least about 200, at least about 300, at least about 500, at least about 1000, at least about 2000, at least about 3000, at least about 5000, at least about 10,000, at least about 20,000, at least about 300,000, or at least about 500,000 entities therein.
the microparticles may also, in some cases, exhibit a relatively uniform distribution of entities per microparticles.
the entities may exhibit a core loading within microparticle such that the entities take up at least about 1%, at least about 50%, at least about 60%, at least about 70%, at least about 75%, at least about 80% at least about 85%, at least about 90%, at least about 95%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or at least about 99.7% of the volume of the interior of the microparticle (i.e., not including the volume of the shell).
the core of the microparticle comprises about 20% continuous phase and about 80% dispersed phase.
the core loading of the dispersed phase may be between about 1% and about 80% of the volume of the interior of the particle. In one embodiment, the core loading of the dispersed phase may be between about 50% and about 70% of the volume of the interior of the particle.
the entities may, in some cases, be relatively monodisperse.
the entities within a microparticle may have an overall average diameter and a distribution of diameters such that no more than about 5%, no more than about 2%, or no more than about 1% of the particles or droplets have a diameter less than about 90% (or less than about 95%, or less than about 99%) and/or greater than about 110% (or greater than about 105%, or greater than about 101%) of the overall average diameter of the plurality of entities.
the entities may not necessarily be relatively monodisperse.
the entities may contain one or more than one agent, in any suitable distribution.
a microparticle may contain a first entity containing a first agent and a second entity containing a second agent, or an entity containing both first and second agents, or the like. If more than one microparticle is present, the microparticles may independently contain the same or different agents, at the same or different concentrations, etc.
any suitable concentration of agent may be present within the entities.
the agent may be present within the entities at a concentration of at least about 0.001 M, at least about 0.003 M, at least about 0.005 M, at least about 0.01 M, at least about 0.03 M, at least about 0.05 M, at least about 0.1 M, at least about 0.3 M, at least about 0.5 M, at least about 1 M, etc.
concentration of agent used may depend, for example, on the particular application.
the systems and methods described herein can be used in a plurality of applications.
fields in which the microparticles described herein may be useful include, but are not limited to, food, beverage, health and beauty aids, paints and coatings, chemical separations, agricultural applications, and drugs and drug delivery.
a precise quantity of a fluid, drug, pharmaceutical, or other agent can be contained in an entity.
Non-limiting examples include biochemical species such as nucleic acids such as siRNA, RNAi and DNA, proteins, peptides, or enzymes.
Additional agents that may be used include, but are not limited to, colloidal particles, magnetic particles, nanoparticles, quantum dots, fragrances, perfumes, proteins, indicators, dyes, fluorescent species, chemicals, biocides, or the like.
Exemplary perfume materials may comprise a material selected from the group consisting of prop-2-enyl 3-cyclohexylpropanoate, (4aR,5R,7aS,9R)-octahydro-2,2,5,8,8,9a-hexamethyl-4h-4a,9-methanoazuleno(5,6-d)-1,3-dioxole, (3aR,5aS,9aS,9bR)-3a,6,6,9a-tetramethyl-2,4,5,5a,7,8,9,9b-octahydro-1H-benzo[e][1]benzofuran, 4-methoxybenzaldehyde, benzyl 2-hydroxybenzoate, 2-methoxynaphthalene, 3-(4-tert-butylphenyl)propanal, 3a,6,6,9a-tetramethyl-2,4,5,5a,7,8,9,9b-octahydro-1H-benzo[e
the agent may comprise a material selected from the group consisting of a small molecule dye, a polymeric dye, a dye clay conjugate, a pigment or mixtures thereof;
the agent may comprise a silicone.
the silicone may comprise a material selected from the group consisting of non-functionalized siloxane polymers, functionalized siloxane polymers, silicone resins, silicone solvents, cyclic silicones and mixtures thereof.
the functionalized siloxane polymers may comprise aminosilicones, amidosilicones, silicone polyethers, silicone-urethane polymers, quaternary ABn silicones, amino ABn silicones, and mixtures thereof.
the non-functionalized siloxane polymer may comprise polydimethylsiloxane, dimethicone, dimethiconol, dimethicone crosspolymer, phenyl trimethicone, alkyl dimethicone, lauryl dimethicone, stearyl dimethicone, phenyl dimethicone, phenylpropyl substituted dimethicone and mixtures thereof.
the silicones may comprise Si—O moieties and may be selected from (a) non-functionalized siloxane polymers, (b) functionalized siloxane polymers, and combinations thereof.
the molecular weight of the organosilicone is usually indicated by the reference to the viscosity of the material.
the organosilicones may have a viscosity at 25 deg. C. of from about 1 cPs to about 2,000,000 cPs, or from about 5 cPs to about 800,000 cPs, or even from about 10 cPs to 300,000 cPs, or even from about 50 cPs to about 50,000 cPs.
suitable organosilicones or mixtures thereof may have a viscosity at 25 deg. C. of from about 10 cPs to about 10,000 cPs, or from about 50 cPs to about 1,000 cPs, or even from about 80 cPs to about 600 cPs.
Silicone materials and silicone resins in particular might conveniently be identified according to a shorthand nomenclature system known to those of ordinary skill in the art as “MDTQ” nomenclature. Under this system, the silicone is described according to presence of various siloxane monomer units which make up the silicone. Briefly, the symbol M denotes the monofunctional unit (CH3)3SiO0.5; D denotes the difunctional unit (CH3)2SiO; T denotes the trifunctional unit (CH3)SiO1.5; and Q denotes the quadra- or tetra-functional unit SiO2. Primes of the unit symbols (e.g. M′, D′, T′, and Q′) denote substituents other than methyl, and must be specifically defined for each occurrence.
MDTQ shorthand nomenclature system known to those of ordinary skill in the art as “MDTQ” nomenclature. Under this system, the silicone is described according to presence of various siloxane monomer units which make up the silicone. Briefly, the symbol M de
Suitable organosilicones may be linear, branched or cross-linked.
the organosilicones may comprise a silicone resin.
Silicone resins are highly cross-linked polymeric siloxane systems. The cross-linking is introduced through the incorporation of trifunctional and tetrafunctional silanes with monofunctional or difunctional, or both, silanes during manufacture of the silicone resin.
SiO“n”/2 represents the ratio of oxygen and silicon atoms.
SiO1/2 means that one oxygen is shared between two Si atoms.
SiO2/2 means that two oxygen atoms are shared between two Si atoms
SiO312 means that three oxygen atoms are shared are shared between two Si atoms.
the organosilicone may comprise polydimethylsiloxane, dimethicone, dimethiconol, dimethicone crosspolymer, phenyl trimethicone, alkyl dimethicone, lauryl dimethicone, stearyl dimethicone, phenyl dimethicone, phenylpropyl substituted dimethicone and mixtures thereof.
the organosilicone may comprise a cyclic silicone.
the cyclic silicone may comprise a cyclomethicone of the formula [(CH3)2SiO]n where n is an integer that may range from about 3 to about 7, or from about 5 to about 6.
the organosilicone may comprise a functionalized siloxane polymer.
Functionalized siloxane polymers may comprise one or more functional moieties selected from the group consisting of amino, amido, alkoxy, hydroxy, polyether, carboxy, hydride, mercapto, sulfate phosphate, and/or quaternary ammonium moieties. These moieties may be attached directly to the siloxane backbone through a bivalent alkylene radical, (i.e., “pendant”) or may be part of the backbone.
a bivalent alkylene radical i.e., “pendant”
Suitable functionalized siloxane polymers include materials selected from the group consisting of aminosilicones, amidosilicones, silicone polyethers, silicone-urethane polymers, quaternary ABn silicones, amino ABn silicones, and mixtures thereof.
Non-limiting examples of suitable silicones are Pulpaid (Registered trademark) 3500, Pulpaid (Registered trademark) 3600, Xiameter (Registered trademark) ACP-0001, Xiameter (Registered trademark) PMX-0245 and Xiameter (Registered trademark) PMX-0246, Dow Corning (Registered trademark) FS 1266 from Dow Corning; Silfoam (Registered trademark) SD 860, Silfoam (Registered trademark) SD 168, Silfoam (Registered trademark) SD 850, Silfoam (Registered trademark) SD 650, Silfoam (Registered trademark) SE 36, Silfoam (Registered trademark) SE 39, Silfoam (Registered trademark) SC 1092, Silfoam (Registered trademark) SC 1132, Silfoam (Registered trademark) SC 129, Silfoam (Registered trademark) SC 132, Silfoam (Registered trademark) SE 47, Silfoam
the agent may be selected from mineral oils, soybean oils, petrolatum, and lanolin.
the agent may include sensates. Exemplary sensates include a composition of menthol and menthyl lactate.
the entities may be contained within a fluid within the microparticles.
the fluid may be any suitable fluid that can contain the entities, e.g., suspended within the fluid.
the fluid may be immiscible with the fluids forming the entities, e.g., where the entities comprise fluids.
suitable fluids include water or other aqueous fluids (such as cell or biological media, salt solutions, alcohol, etc.), or hydrophobic fluids.
hydrophobic liquids include, but are not limited to, oils such as hydrocarbons, silicone oils, mineral oils, fluorocarbon oils, organic solvents etc.
the fluid may be one in which the agent within the entities does not easily dissolve or other pass through, e.g., to reach the shell of the microparticle. If the agent has relatively low solubility within the fluid, then relatively large amounts or concentrations of agent may be contained within the entities, relative to the fluid. Thus, for example, even if there is a relatively low concentration of agent that can be contained within the fluid, the microparticle may exhibit surprisingly high amounts of the agent therein, if one were to assume that the microparticle were only filled with the fluid.
the rate-limiting step for the release of agent from the microparticle may be controlled by the rate of dissolution of the agent within the fluid, rather than by the maximum concentration of agent within the fluid, since much of the agent may be stored within the entities instead of within the fluid itself.
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 emulsion is produced.
two fluids may be selected to be immiscible within the time frame of the formation of the fluidic droplets.
the microparticle may also contain a shell surrounding the fluid and the entities, in certain aspects.
the shells can comprise a polymer in some embodiments. Examples include, but are not limited to, ethoxylated trimethylolpropane triacrylate (ETPTA), polystyrene, polycaprolactone, polyisoprene, poly(lactic acid), polystyrene (PS), polycaprolactone (PCL), polyisoprene (PIP), poly(lactic acid), polyethylene, polypropylene, polyacrylonitrile, polyimide, polyamide, poly(normal-butyl acrylate)-poly(acrylic acid), and/or mixtures and/or co-polymers of these and/or other polymers.
ETPTA ethoxylated trimethylolpropane triacrylate
PEPTA polystyrene
polycaprolactone polyisoprene
PS polystyrene
PCL polycaprolactone
PIP
the shell material may comprise, poly(vinyl alcohol), poly(vinyl acetate), poly(vinyl pyrrolidone), poly(vinyl acetate phthalate), vinyl acetate neodecanoic acid co-polymer, vinyl acetate ethylene co-polymer, vinyl acetate crotonic acid neodecanoate co-polymer, vinyl acetate crotonic acid co-polymer, vinyl acetate butyl maleate co-polymer, cellulose acetate, cellulose acetate phathalate, ethyl cellulose, hydroxyl propyl methyl cellulose phathalate, cellulose acetate butyrate, vinyl pyrrolidone vinyl acetate co-polymer, poly(styrene-co-maleic acid) isobutyl ester, poly(styrene-co-butadiene), poly(styrene-co-acrylic) and mixtures thereof.
shell materials may comprise Vinavil® VIN, Vinavil® 6915, Vinavil® 03V, Vinavil EVA® 04 and Vinaflex® CR50 from Vinavil S.p.A., Italy; Luviset® CAN, Luviset® CA66 and Luviskol® VA 37 E from BASF, Germany; Sureteric® and Ethocel, Et from Colorcon, U.S.A.; Mowiol® grades from Sigma-Aldrich; Antaron-Ganex® V-220 F and Antaron-Ganex® WP-660 from ISP Chemicals, or mixtures thereof.
said core and/or said shell may comprise a viscosity regulator.
said viscosity regulator may comprise a water-soluble solvent, a water-insoluble solvent, silicones, perfume raw materials and/or mixtures thereof.
microparticles described herein may have any suitable average cross-sectional diameter.
Those of ordinary skill in the art will be able to determine the average cross-sectional diameter of a single and/or a plurality of particles, for example, using laser light scattering, microscopic examination, or other known techniques.
the average cross-sectional diameter of a single particle, in a non-spherical particle is the diameter of a perfect sphere having the same volume as the non-spherical particle.
the average cross-sectional diameter of a particle 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, or between about 50 micrometers and about 1 mm, between about 10 micrometers and about 500 micrometers, or between about 50 micrometers and about 100 micrometers in some cases.
the average cross-sectional 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. In some embodiments, at least about 50%, at least about 75%, at least about 90%, at least about 95%, or at least about 99% of the particles or droplets within a plurality of particles or droplets has an average cross-sectional diameter within any of the ranges outlined in this paragraph.
Certain applications may use a plurality of particles, at least some of which contain a fluid and entities such as those described herein.
Some embodiments of the invention advantageously employ microparticles with relatively consistent properties.
a plurality of particles is provided wherein the distribution of thicknesses of the outermost layer among the plurality of particles is relatively uniform.
a plurality of particles is provided having an overall thickness, measured as the average of the average thicknesses of each of the plurality of particles.
the distribution of the average thicknesses can be such that no more than about 5%, no more than about 2%, or no more than about 1% of the particles or droplets have an outermost layer with an average thickness thinner than 90% (or thinner than 95%, or thinner than 99%) of the overall average thickness and/or thicker than 110% (or thicker than 105%, or thicker than about 101%) of the overall average thickness of the outermost layer.
the microparticles may comprise relatively thick shells.
Exemplary shell thicknesses for such embodiments include thicknesses ranging from between about 0.1 ⁇ m to about 10 ⁇ m.
the shell wall thicknesses of a population of the particles may have a mean of between about wtmm ⁇ m to about wthmM ⁇ m.
the microparticles may comprise relatively thin outer shells.
Techniques for forming relatively thin outer shells include those discussed in U.S. Provisional Application Ser. No. 61/980,541, filed Apr. 16, 2014, entitled “Systems and Methods for Producing Droplet Emulsions with Relatively Thin Shells”; or in U.S. Pat. Apl. Pub. No. 2014-0220350, entitled “Multiple Emulsions and Techniques for the Formation of Multiple Emulsions,” published Aug. 7, 2014, each incorporated herein by reference in its entirety.
the shell may have an average thickness (i.e., between the first fluid and the second fluid) of less than about 1 micrometer, less than about 500 nm, less than about 300 nm, less than about 200 nm, less than about 100 nm, less than about 50 nm, less than about 30 nm, less than about 20 nm, or less than about 10 nm.
the thickness may be determined optically or visually, or in some cases, estimated based on the volumes and/or flow rates of fluid entering or leaving a conduit. If the droplet is non-spherical, then average thickness or diameters may be determined using the diameter of a perfect sphere having the same volume as the non-spherical droplet(s).
the volumes or thicknesses of a layer of fluid in a droplet may be determined or estimated (e.g., before and/or after distortion) using any suitable technique, e.g., visually or optically.
the volumes or thickness of a layer of fluid may be estimated statistically, e.g., by determining the amount of fluid present in the microparticles.
the thickness may be determined as a percentage of the diameter of the overall droplet within the carrying fluid.
the thickness of the shell of the microparticle may be than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 3%, less than about 1%, less than about 0.5%, less than about 0.3%, or less than about 0.1% of the diameter of the overall droplet.
the shell may comprise a relatively small percentage by volume of the overall microparticle.
the shell may comprise less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 3%, less than about 1%, less than about 0.5%, less than about 0.3%, or less than about 0.1% of the overall droplet.
the shell may have a thickness such that the difference between the average diameter of the shell and the average diameter of the interior of the shell (including fluid and any entities therein) is less than about 20% of the average diameter of the overall droplet, and in some cases, less than about 15%, less than about 10%, less than about 5%, less than about 3%, less than about 1%, less than about 0.5%, less than about 0.3%, or less than about 0.1% of the average diameter of the overall microparticle.
the shell may have an average thickness of less than about 0.05, less than about 0.01, less than about 0.005, or less than about 0.001 times the average cross-sectional diameter of the microparticle, or between about 0.0005 and about 0.05, between about 0.0005 and about 0.01, between about 0.0005 and about 0.005, or between about 0.0005 and about 0.001 times the average cross-sectional diameter of the microparticle.
the shell may have an average thickness of less than about 1 micron, less than about 500 nm, or less than about 100 nm, or between about 50 nm and about 1 micron, between about 50 nm and about 500 nm, or between about 50 nm and about 100 nm
SEM scanning electron microscope
the interior of the shell (including fluid and any entities therein) is relatively large, e.g., a large percentage of the volume of the microparticle is taken up by the interior, which may result in the shell having a relatively thin thickness.
the interior may take up at least about 80% of the volume of the microparticle, and in some cases, at least about 85%, at least about 90%, at least about 95%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or at least about 99.7% of the volume of the microparticle.
the diameter of the interior may be at least about 80% of the diameter of the microparticle, and in some cases, at least about 85%, at least about 90%, at least about 95%, at least about 97%, at least about 98%, at least about 99%, at least about 99.5%, or at least about 99.7% of the diameter of the microparticle.
the interior comprises at least about 50% of the volume of the microparticle, and in some cases, at least about 60%, at least about 70%, at least about 75%, at least about 80%, or at least about 85% of the volume of the microparticle.
the volume of the interior may also be no more than about 90%, no more than about 85%, no more than about 80%, no more than about 75%, no more than about 70%, no more than about 65%, no more than about 60%, or no more than about 55% of the volume of the microparticle. Combinations of any of these are also possible, e.g., the interior may comprise between about 50% and about 80% of the volume of the microparticle.
the microparticles may have relatively uniform cross-sectional diameters in certain embodiments.
the use of particles with relatively uniform cross-sectional diameters can allow one to control viscosity, the amount of species delivered to a target, and/or other parameters of the delivery of fluid and/or species from the particles.
the particles are relatively monodisperse, or the plurality of particles has an overall average diameter and a distribution of diameters such that no more than about 5%, no more than about 2%, or no more than about 1% of the particles or droplets have a diameter less than about 90% (or less than about 95%, or less than about 99%) and/or greater than about 110% (or greater than about 105%, or greater than about 101%) of the overall average diameter of the plurality of particles.
the microparticles has an overall average diameter and a distribution of diameters such that the coefficient of variation of the cross-sectional diameters of the particles or droplets is less than about 10%, less than about 5%, less than about 2%, between about 1% and about 10%, between about 1% and about 5%, or between about 1% and about 2%.
the coefficient of variation can be determined by those of ordinary skill in the art, and may be defined as:
⁇ is the standard deviation and ⁇ is the mean.
the microparticles may be exposed to an environment to which the agent is to be released.
the environment may be any suitable environment, and can be, e.g., a liquid or a gas.
the agent may be releasable from the microparticles, in some embodiment, without significantly damaging or disrupting the microparticles, e.g., by damaging the shell of the microparticles to cause release of the agent.
the agent may be diffuse across the outer shell of the microparticles to be released externally of the microparticles.
the agent may exit the microparticles passively, or the microparticles may be treated in some way to cause release of the agent.
the agent may be released by agitating the microparticles, e.g., intermittently or continuously.
the microparticles may be exposed to a fluid, such as oil or water.
the agent may be soluble in oil or water, such that upon reaching the surface of the microparticle, the agent can readily enter the fluid.
relatively high amounts of agent may be released from the microparticles into the surrounding environment, e.g., without damaging the microparticles. For instance, at least about 30 wt %, at least about 50 wt %, at least about 60 wt %, at least about 70 wt %, at least about 75 wt %, at least about 80 wt %, at least about 85 wt %, at least about 90 wt %, or at least about 95 wt % of the agent may be released from the microparticles upon exposure to a suitable surrounding environment.
the rate of release of agent from the microparticles may be controlled, e.g., based on the ability of the agent to exit the entities contained within the microparticles and pass through the internal fluid and the shell of the microparticles.
the amount of loading of entities within the microparticles, and the rate at which the agent is released from the microparticles may not necessarily be coupled to each other.
the fluid surrounding the entities may act as a rate-limiting step (e.g., if the agent is not fully soluble within the fluid), and the entities may thus act as a “reservoir” to contain the agent prior to release from the microparticles.
microfluidic conduits can be positioned to create the multiple emulsion droplets, e.g., in series. In some cases, e.g., by controlling the flow of a fluid through a conduit, surprisingly thin inner layers of fluid may be created.
a first conduit may be used to inject a first fluid into a second fluid that is immiscible with the first fluid.
the first fluid may contain entities therein, e.g. suspended therein.
the first fluid may comprise an emulsion having continuous and dispersed phases.
the dispersed phase may be immiscible in the continuous phase but substantially miscible in the second fluid, or polymers which may be formed from the second fluid.
the entities may also contain an agent for subsequent release from the microparticles.
the entities may be contained within the first fluid in any suitable amount or concentration, including those described above with respect to the final amount or concentration within the microparticles.
the first conduit may end at an exit opening.
the first conduit may gradually or suddenly reach the diameter of the exit opening.
a tapered region may be used.
the length of the tapered region may be any suitable length as determined in the direction of average fluid flow within the channel; for example, the length can be less than about 1 mm, less than about 500 micrometers, less than about 300 micrometers, less than about 100 micrometers, less than about 50 micrometers, less than about 30 micrometers, less than about 10 micrometers, etc.
the first conduit may have a cross-sectional dimension of 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, or other dimensions as discussed herein.
the cross-sectional area of the first conduit may vary.
the first conduit is substantially smaller than the second conduit at the point where the first conduit opens into a second conduit.
the first conduit may have a cross-sectional area of the exit opening that is no more than about 75%, no more than about 50%, no more than about 45%, no more than about 40%, no more than about 35%, no more than about 30%, no more than about 25%, no more than about 20%, no more than about 15%, no more than about 10%, or no more than about 5% of the cross-sectional area of the second conduit at that location.
the first fluid containing entities, e.g., as discussed above
the first fluid may encounter a second fluid and a third fluid contained within a second conduit.
the second fluid may be immiscible with the first fluid and/or the third fluid, in some cases.
the second fluid may be caused to form droplets surrounding the first fluid (and entities) contained within the third fluid.
the second and third fluids may be introduced into the second conduit in directions substantially opposed to each other. The droplets may be formed prior to entering the third conduit or while the combination of fluids is passing through the third conduit.
the second conduit may have a cross-sectional dimension of 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, or other dimensions as discussed herein.
the cross-sectional area of the second conduit may be substantially constant, or may vary.
the second conduit may be tapered.
the droplets may then exit the second conduit through an entrance opening of a third conduit, e.g., to be polymerized, or for subsequent use, etc.
a third conduit e.g., to be polymerized, or for subsequent use, etc.
one or more of the fluids may be hardened as discussed below to form a particle.
the particle may have the same dimensions as the droplet prior to hardening.
the third conduit may have a cross-sectional dimension of 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, or other dimensions as discussed herein.
the cross-sectional area of the third conduit may be substantially constant, or may vary.
the third conduit may be tapered.
the third conduit is substantially smaller than the second conduit at the entrance opening to the third conduit.
the third conduit may have a cross-sectional area of the exit opening that is no more than about 75%, no more than about 50%, no more than about 45%, no more than about 40%, no more than about 35%, no more than about 30%, no more than about 25%, no more than about 20%, no more than about 15%, no more than about 10%, or no more than about 5% of the cross-sectional area of the third conduit at that location.
the third conduit may have a diameter that changes moving away from the entrance opening, although in other cases, the diameter of the third conduit may be substantially constant.
Some benefit agents and/or shell material solutions might have a high viscosity after dissolution or dispersion, so certain additives as viscosity regulators might be added to the core and/or the shell as processing aid to facilitate the flow of such benefit agents and/or shell materials through the conduits.
Such viscosity regulators may comprise water-soluble solvents, water-insoluble solvents, perfume raw materials, silicones and/or mixtures thereof.
Non-limiting examples include ethanol, propanol, isopropanol, n-propanol, n-butanol, t-butanol, propylene glycol, 1,3-propanediol, ethylene glycol, diethylene glycol, dipropylene glycol, 1,2,3-propanetriol, propylene carbonate, phenylethyl alcohol, 2-methyl 1,3-propanediol, hexylene glycol, glycerol, sorbitol, polyethylene glycols, 1,2-hexanediol, 1,2-pentanediol, 1,2-butanediol, 1,4 butanediol, 1,4-cyclohexanedimethanol, pinacol, 1,5-hexanediol, 1,6-hexanediol, 2,4-dimethyl-2,4-pentanediol, 2,2,4-trimethyl-1,3-pent
the outer, second fluid surrounding the droplets may be hardened to form microparticles, e.g., containing the first fluid and the entities.
light such as ultraviolet light
the third fluid may contain a chemical that can react with the second fluid (e.g., at its surface) to harden the second fluid.
certain changes such as temperature changes, may be used to induce hardening of the second fluid to form microparticles.
a fluid may be dried, gelled, and/or polymerized, and/or otherwise solidified, e.g., to form a solid, or at least a semi-solid.
the solid that is formed may be rigid in some embodiments, although in other cases, the solid may be elastic, rubbery, deformable, etc.
an outermost layer of fluid may be solidified to form a solid shell at least partially containing an interior containing a fluid and/or a species. Any technique able to solidify at least a portion of a fluidic droplet can be used.
a fluid within a fluidic droplet may be removed to leave behind a material (e.g., a polymer) capable of forming a solid shell.
a fluidic droplet may be cooled to a temperature below the melting point or glass transition temperature of a fluid within the fluidic droplet, a chemical reaction may be induced that causes at least a portion of the fluidic droplet to solidify (for example, a polymerization reaction, a reaction between two fluids that produces a solid product, etc.), or the like.
Other examples include pH-responsive or molecular-recognizable polymers, e.g., materials that gel upon exposure to a certain pH, or to a certain species.
a fluidic droplet is solidified by increasing the temperature of the fluidic droplet. For instance, a rise in temperature may drive out a material from the fluidic droplet (e.g., within the outermost layer of a multiple emulsion droplet) and leave behind another material that forms a solid. Thus, in some cases, an outermost layer of a multiple emulsion droplet may be solidified to form a solid shell that encapsulates entities contained within a fluid.
photoinitiators may include benzyl ketones, monomeric hydroxyl ketones, polymeric hydroxyl ketones, alpha-amino ketones, acyl phosphine oxides, metallocenes, benzophenone, benzophenone derivatives, and many others as described in (US 20140261508 A1),
Exemplary photoinitiators include: Benzoin Ethyl Ether, 2-hydroxy-2-Methylphenylpropanone, Irgacure 369, Irgacure LEX 201, Irgacure 819, Darocur 4265, Irgacure 184, Irgacure 2959, and the visible light initiator: Irgacure 784, Camphorquinone(GENOCURE* CQ).
Acrylate and acrylamide can also be cured thermally by adding thermal initiator as described in patent publication: WO 2011084141 A2(Appleton).
the initiators are energy activated meaning free radicals are generated when the initiators are subjected to heat or other energy input.
initiators include peroxy initiators, azo initiators, peroxides, and compounds such as 2,2′-azobismethylbutyronitrile, dibenzoyl peroxide.
the free radical initiator can be selected from the group of initiators comprising an azo or peroxy initiator, such as peroxide, dialkyl peroxide, alkyl peroxide, peroxyester, peroxycarbonate, peroxyketone and peroxydicarbonate, 2,2′-azobis(isobutylnitrile), 2,2′-azobis(2,4-dimethylpentanenitrile), 2,2′-azobis(2,4-dimethylvaleronitrile), 2,2′-azobis(2-methylpropanenitrile), 2,2′-azobis(methylbutyronitrile), 1,1′-azobis(cyclohexanecarbonitrile), 1,1′-azobis(cyanocyclohexane), benzoyl peroxide, decanoyl peroxide; lau
initiators typically indicate a decomposition temperature for the initiator.
the initiator is selected to have a decomposition point of about 50° C. or higher.
Multiple initiators may be employed, either as a blend in the oil phase, or in either of the oil or water phases.
initiators are selected to stagger the decomposition temperatures at the various steps, pre-polymerization, wall formation and hardening or polymerizing of the capsule wall material.
a first initiator in the oil phase can decompose at 55° C., to promote prepolymer formation; a second can decompose at 60° C. to aid forming the wall material.
a third initiator can decompose at 65° C. to facilitate polymerization of the capsule wall material.
the total amount of initiator can be typically as low as 0.1 weight percent or as high as 10 weight percent.
the microparticles are prepared in a microfluidic system.
“Microfluidic,” as used herein, 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 channels of the system may be a capillary tube. In some cases, multiple channels are provided, and in some embodiments, at least some are nested, as described herein.
the channels 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.
the cross-section of one or more of the channels may, have a height that is substantially the same as a width at the same point. In cross-section, the channels may be rectangular or substantially non-rectangular, such as circular or elliptical.
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.
the fluid is a liquid.
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.
a variety of materials and methods, according to certain aspects of the invention, can be used to form articles or components such as those described herein, e g, channels such as microfluidic channels, chambers, etc.
various articles or 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, 3D printing, and the like. See, for example, Scientific American, 248:44-55, 1983 (Angell, et al).
various structures or components of the articles described herein can be formed from glass or a polymer, for example, an elastomeric polymer such as polydimethylsiloxane (“PDMS”), polytetrafluoroethylene (“PTFE” or Teflon®), epoxy, norland optical adhesive, or the like.
PDMS polydimethylsiloxane
PTFE polytetrafluoroethylene
microfluidic channels may be formed from glass tubes or capillaries.
a microfluidic channel may be implemented by fabricating the fluidic system separately using PDMS or other soft lithography techniques (details of soft lithography techniques suitable for this embodiment are discussed in the references entitled “Soft Lithography,” by Younan Xia and George M.
various structures or components of the articles described herein can be formed of a metal, for example, stainless steel.
polymers include, but are not limited to, polyethylene terephthalate (PET), polyacrylate, polymethacrylate, polycarbonate, polystyrene, polyethylene, polypropylene, polyvinylchloride, cyclic olefin copolymer (COC), polytetrafluoroethylene, a fluorinated polymer, a silicone such as polydimethylsiloxane, polyvinylidene chloride, bis-benzocyclobutene (“BCB”), a polyimide, a fluorinated derivative of a polyimide, or the like. Combinations, copolymers, or blends involving polymers including those described above are also envisioned.
the device may also be formed from composite materials, for example, a composite of a polymer and a semiconductor material.
various structures or components of the article 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, waxes, or mixtures or composites thereof 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.
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, dodecyltrichlorosilanes, etc.
Silicone polymers are used in certain 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, Mich., and particularly Sylgard 182, Sylgard 184, and Sylgard 186.
Silicone polymers including PDMS have several beneficial properties simplifying fabrication of various 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.
silicone polymers such as PDMS
PDMS can be elastomeric and thus may be useful for forming very small features with relatively high aspect ratios, necessary in certain embodiments of the invention.
Flexible (e.g., elastomeric) molds or masters can be advantageous in this regard.
One advantage of forming structures such as microfluidic structures or channels 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.
structures can be fabricated and then oxidized and essentially irreversibly sealed to other silicone polymer surfaces, or to the surfaces of other substrates reactive with the oxidized silicone polymer surfaces, without the need for separate adhesives or other sealing means.
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.
a base portion including a bottom wall and side walls can be fabricated from an opaque material such as silicon or PDMS, and 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, e.g., as discussed herein.
Material used to fabricate various components of the systems and devices of the invention 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.
a non-limiting example of such a coating is disclosed below; additional examples are disclosed in Int. Pat. Apl. Ser. No. PCT/US2009/000850, filed Feb. 11, 2009, entitled “Surfaces, Including Microfluidic Channels, With Controlled Wetting Properties,” by Weitz, et al., published as WO 2009/120254 on Oct. 1, 2009, 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 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 comprises the surface of a silicon wafer or microchip, or other substrate.
Other components may, 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 may 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 design and/or fabrication of the article may be relatively simple, e.g., by using relatively well-known soft lithography and other techniques such as those described herein.
rapid and/or customized design of the article is possible, for example, in terms of geometry.
the article may be produced to be disposable, for example, in embodiments where the article is used with substances that are radioactive, toxic, poisonous, reactive, biohazardous, etc., and/or where the profile of the substance (e.g., the toxicology profile, the radioactivity profile, etc.) is unknown.
channels or other structures can be much more hydrophilic than the surfaces of typical elastomeric polymers (where a hydrophilic interior surface is desired).
Such hydrophilic channel surfaces can thus be more easily filled and wetted with aqueous solutions than can structures comprised of typical, unoxidized elastomeric polymers or other hydrophobic materials.
one or more of the channels within the device may be relatively hydrophobic or relatively hydrophilic, e.g. inherently, and/or by treating one or more of the surfaces or walls of the channel to render them more hydrophobic or hydrophilic.
the fluids that are formed into droplets in the device are substantially immiscible, at least on the time scale of forming the droplets, and the fluids will often have different degrees of hydrophobicity or hydrophilicity.
a first fluid may be more hydrophilic (or more hydrophobic) relative to a second fluid, and the first and the second fluids may be substantially immiscible.
the first fluid can from a discrete droplet within the second fluid, e.g., without substantial mixing of the first fluid and the second fluid (although some degree of mixing may nevertheless occur under some conditions).
the second fluid may be more hydrophilic (or more hydrophobic) relative to a third fluid (which may be the same or different than the first fluid), and the second and third fluids may be substantially immiscible.
a surface of a channel may be relatively hydrophobic or hydrophilic, depending on the fluid contained within the channel.
a surface of the channel is hydrophobic or hydrophilic relative to other surfaces within the device.
a relatively hydrophobic surface may exhibit a water contact angle of greater than about 90°, and/or a relatively hydrophilic surface may exhibit a water contact angle of less than about 90°.
relatively hydrophobic and/or hydrophilic surfaces may be used to facilitate the flow of fluids within the channel, e.g., to maintain the nesting of multiple fluids within the channel in a particular order.
emulsions such as those described herein may be prepared by controlling the hydrophilicity and/or hydrophobicity of the channels used to form the emulsion.
the hydrophilicity and/or hydrophobicity of the channels may be controlled by coating a sol-gel onto at least a portion of a channel.
relatively hydrophilic and relatively hydrophobic portions may be created by applying a sol-gel to portions of the channel surfaces, which renders those portions relatively hydrophobic.
the sol-gel may comprise an initiator, such as a photoinitiator.
Portions may be rendered relatively hydrophilic by filling the channels with a solution containing a hydrophilic moiety (for example, acrylic acid), and exposing the portions to a suitable trigger for the initiator (for example, light or ultraviolet light in the case of a photoinitiator).
a suitable trigger for the initiator for example, light or ultraviolet light in the case of a photoinitiator.
the portions may be exposed by using a mask to shield portions in which no reaction is desired, by directing a focused beam of light or heat onto the portions in which reaction is desired, or the like.
the initiator may cause the reaction (e.g., polymerization) of the hydrophilic moiety to the sol-gel, thereby rendering those portions relatively hydrophilic (for instance, by causing poly(acrylic acid) to become grafted onto the surface of the sol-gel coating in the above example).
the reaction e.g., polymerization
a sol-gel is a material that can be in a sol or a gel state, and typically includes polymers.
the gel state typically contains a polymeric network containing a liquid phase, and can be produced from the sol state by removing solvent from the sol, e.g., via drying or heating techniques.
the sol may be pretreated before being used, for instance, by causing some polymerization to occur within the sol.
the sol-gel coating may be chosen to have certain properties, for example, having a certain hydrophobicity.
the properties of the coating may be controlled by controlling the composition of the sol-gel (for example, by using certain materials or polymers within the sol-gel), and/or by modifying the coating, for instance, by exposing the coating to a polymerization reaction to react a polymer to the sol-gel coating, as discussed below.
the sol-gel coating may be made more hydrophobic by incorporating a hydrophobic polymer in the sol-gel.
the sol-gel may contain one or more silanes, for example, a fluorosilane (i.e., a silane containing at least one fluorine atom) such as heptadecafluorosilane, or other silanes such as methyltriethoxy silane (MTES) or a silane containing one or more lipid chains, such as octadecylsilane or other CH 3 (CH 2 ) n -silanes, where n can be any suitable integer. For instance, n may be greater than 1, 5, or 10, and less than about 20, 25, or 30.
a fluorosilane i.e., a silane containing at least one fluorine atom
MTES methyltriethoxy silane
n can be any suitable integer.
n may be greater than 1, 5, or 10, and less than about 20, 25, or
the silanes may also optionally include other groups, such as alkoxide groups, for instance, octadecyltrimethoxysilane.
groups such as alkoxide groups, for instance, octadecyltrimethoxysilane.
silanes can be used in the sol-gel, with the particular silane being chosen on the basis of desired properties such as hydrophobicity.
Other silanes e.g., having shorter or longer chain lengths
the silanes may contain other groups, for example, groups such as amines, which would make the sol-gel more hydrophilic.
Non-limiting examples include diamine silane, triamine silane, or N-[3-(trimethoxysilyl)propyl]ethylene diamine silane.
the silanes may be reacted to form oligomers or polymers within the sol-gel, and the degree of polymerization (e.g., the lengths of the oligomers or polymers) may be controlled by controlling the reaction conditions, for example by controlling the temperature, amount of acid present, or the like.
more than one silane may be present in the sol-gel.
the sol-gel may include fluorosilanes to cause the resulting sol-gel to exhibit greater hydrophobicity, and other silanes (or other compounds) that facilitate the production of polymers.
materials able to produce SiO 2 compounds to facilitate polymerization may be present, for example, TEOS (tetraethyl orthosilicate).
the sol-gel is not limited to containing only silanes, and other materials may be present in addition to, or in place of, the silanes.
the coating may include one or more metal oxides, such as SiO 2 , vanadia (V 2 O 5 ), titania (TiO 2 ), and/or alumina (Al 2 O 3 ).
the microfluidic channel is present in a material suitable to receive the sol-gel, for example, glass, metal oxides, or polymers such as polydimethylsiloxane (PDMS) and other siloxane polymers.
the microfluidic channel may be one which contains silicon atoms, and in certain instances, the microfluidic channel may be chosen such that it contains silanol (Si—OH) groups, or can be modified to have silanol groups.
the microfluidic channel may be exposed to an oxygen plasma, an oxidant, or a strong acid to cause the formation of silanol groups on the microfluidic channel.
the sol-gel may be present as a coating on the microfluidic channel, and the coating may have any suitable thickness.
the coating may have a thickness of no more than about 100 micrometers, no more than about 30 micrometers, no more than about 10 micrometers, no more than about 3 micrometers, or no more than about 1 micrometer. Thicker coatings may be desirable in some cases, for instance, in applications in which higher chemical resistance is desired. However, thinner coatings may be desirable in other applications, for instance, within relatively small microfluidic channels.
the hydrophobicity of the sol-gel coating can be controlled, for instance, such that a first portion of the sol-gel coating is relatively hydrophobic, and a second portion of the sol-gel coating is relatively hydrophilic.
the hydrophobicity of the coating can be determined using techniques known to those of ordinary skill in the art, for example, using contact angle measurements such as those discussed herein.
a first portion of a microfluidic channel may have a hydrophobicity that favors an organic solvent to water, while a second portion may have a hydrophobicity that favors water to the organic solvent.
a hydrophilic surface is one that has a water contact angle of less than about 90° while a hydrophobic surface is one that has a water contact angle of greater than about 90°.
the hydrophobicity of the sol-gel coating can be modified, for instance, by exposing at least a portion of the sol-gel coating to a polymerization reaction to react a polymer to the sol-gel coating.
the polymer reacted to the sol-gel coating may be any suitable polymer, and may be chosen to have certain hydrophobicity properties.
the polymer may be chosen to be more hydrophobic or more hydrophilic than the microfluidic channel and/or the sol-gel coating.
a hydrophilic polymer that could be used is poly(acrylic acid).
the polymer may be added to the sol-gel coating by supplying the polymer in monomeric (or oligomeric) form to the sol-gel coating (e.g., in solution), and causing a polymerization reaction to occur between the polymer and the sol-gel.
free radical polymerization may be used to cause bonding of the polymer to the sol-gel coating.
a reaction such as free radical polymerization may be initiated by exposing the reactants to heat and/or light, such as ultraviolet (UV) light, optionally in the presence of a photoinitiator able to produce free radicals (e.g., via molecular cleavage) upon exposure to light.
UV ultraviolet
the photoinitiator may be included with the polymer added to the sol-gel coating, or in some cases, the photoinitiator may be present within the sol-gel coating.
a photoinitiator may be contained within the sol-gel coating, and activated upon exposure to light.
the photoinitiator may also be conjugated or bonded to a component of the sol-gel coating, for example, to a silane.
a photoinitiator such as Irgacur 2959 may be conjugated to a silane-isocyanate via a urethane bond, where a primary alcohol on the photoinitiator may participate in nucleophilic addition with the isocyanate group, which may produce a urethane bond.
the monomer and/or the photoinitiator may be exposed to only a portion of the microfluidic channel, or the polymerization reaction may be initiated in only a portion of the microfluidic channel.
a portion of the microfluidic channel may be exposed to light, while other portions are prevented from being exposed to light, for instance, by the use of masks or filters, or by using a focused beam of light. Accordingly, different portions of the microfluidic channel may exhibit different hydrophobicities, as polymerization does not occur everywhere on the microfluidic channel.
the microfluidic channel may be exposed to UV light by projecting a de-magnified image of an exposure pattern onto the microfluidic channel.
small resolutions e.g., 1 micrometer, or less
projection techniques may be achieved by projection techniques.
the release of the active agent may be facilitated by mechanical rupture of the microparticles, by thermal breakdown of the shell and hydrogel, or by dissolving the shell and hydrogel of the core of the microparticles.
the density mismatch between the payload and the aqueous continuous phase of the first liquid may result in the dispersed payload rising and directly contacting the inner surface of the polymeric shell. This contact may enable the payload to move into the hydrophobic polymer, leading to a rapid leakage and hence limiting the long-term storage of the payload.
the continuous phase of the first liquid may be modified by the addition of a hydrogel precursor and a photo-initiator to enable the conversion of the continuous phase within the microparticles to a hydrogel, enabling it to act as a physical barrier and preventing direct exposure of the innermost dispersed phase payload with the polymeric shell.
Certain aspects of the invention are generally directed to techniques for scaling up or “numbering up” devices such as those discussed herein.
relatively large numbers of devices may be used in parallel, for example at least about 10 devices, at least about 30 devices, at least about 50 devices, at least about 75 devices, at least about 100 devices, at least about 200 devices, at least about 300 devices, at least about 500 devices, at least about 750 devices, or at least about 1,000 devices or more may be operated in parallel.
an array of such devices may be formed by stacking the devices horizontally and/or vertically.
the devices may be commonly controlled, or separately controlled, and can be provided with common or separate sources of various fluids, depending on the application.
a fluid distributor can be used to distribute fluid from one or more inputs to a plurality of outputs, e.g., in one more devices.
a plurality of articles may be connected in three dimensions.
channel dimensions are chosen that allow pressure variations within parallel devices to be substantially reduced.
suitable techniques include, but are not limited to, those disclosed in International Patent Application No. PCT/US2010/000753, filed Mar. 12, 2010, entitled “Scale-up of Microfluidic Devices,” by Romanowsky, et al., published as WO 2010/104597 on Nov. 16, 2010, incorporated herein by reference in its entirety.
an apparatus 1000 for producing microcapsules may include: a first reservoir 100 containing a first liquid, wherein the first liquid may comprise an emulsion comprising in turn, a dispersed phase and a continuous phase.
the first reservoir may be disposed in fluid communication with a plurality of first conduits forming a portion of a plurality of microfluidic devices 600 , each of the first conduits having an exit.
the apparatus also comprises a second reservoir 200 containing a second liquid, the second reservoir may be disposed in fluid communication with a plurality of second conduits forming a portion of the plurality of microfluidic devices 600 .
Each of the second conduits at least partly surrounds one of the first conduits.
the first and second fluids are substantially immiscible.
the apparatus further comprises a third reservoir 300 containing a third liquid, the third reservoir disposed in fluid communication with second conduits.
the second and third fluids being substantially immiscible.
the apparatus further comprising a plurality of third conduits disposed at least in part within the second conduits downstream of the exits of the first conduits as part of the plurality of microfluidic devices, the third conduits positioned to receive the first liquid exiting the first conduits, the second liquid and the third liquid.
the volume of the reservoirs may range from as little as about 2 ml, to as much as about 6,000 L depending upon the volume of product desired to be produced.
the first reservoir may be disposed in switchable fluid communication with the first conduits and the apparatus may further comprise a fourth reservoir 400 containing a fourth liquid, wherein the fourth liquid is an emulsion comprising a dispersed phase and a continuous phase, the fourth reservoir 400 disposed in switchable fluid communication with the first conduits by the activation of valve 500 .
the dispersed phase of the first liquid is substantially miscible with the second liquid and the dispersed phase of the fourth liquid is substantially immiscible with the second liquid.
encapsulated benefit agents need to be isolated from the product before using the methods below and isolation will depend not only on the type and form of the product but also on the encapsulated benefit agent shell nature.
encapsulated benefit agents comprised in a liquid product might be isolated by centrifugation and redisperse in a non-solvent for the encapsulated benefit agent shell, whilst for encapsulated benefit agents comprised in solid products, a solvent for the binder and non-solvent for the encapsulated benefit agent shell might be use.
a population of encapsulated benefit agents is characterized by a mean diameter (D) obtained using scanning electron microscopy and computerized image analysis with the ImageJ software program version 1.46r (Rasband, W. S., ImageJ, U. S. National Institutes of Health, Bethesda, Md., USA, http://imagej.nih gov/ij/, 1997-2012.).
a population of encapsulated benefit agents is characterized by a diameter coefficient of variation (CoV) corresponding to the ratio between the diameter distribution of said population of encapsulated benefit agents (ie the standard deviation) and the mean encapsulated benefit agent diameter.
CoV is obtained as follow:
the mean shell thickness is determined by preparing cross-sections of targeted encapsulated benefit agents and measuring the shell thickness under a Scanning Electron Microscope (such as model JSM-6400, available from JEOL Ltd, Tokyo, Japan). Approximately 200 mg of encapsulated benefit agent sample (as dry powder) is mixed with about 1 mL of Optimal Cutting Temperature solution (OCT).
OCT Optimal Cutting Temperature solution
the OCT solution can be composed of 10.24% poly vinyl alcohol, 4.26% Poly ethylene glycol and 85.5% non-reactive ingredients.
the OCT solution can be comprised of Poly Propylene Glycol, Poly Ethylene Glycol, Glycerin, Vegetable oil and/or Mineral oil.
This OCT solution containing the encapsulated benefit agents suspended in it is immediately frozen by using liquid Nitrogen ( ⁇ 196° C.) and is placed inside a cryostat microtome cooled to ⁇ 20° C.
the cryostat microtome is used to cut sample cross-sections of the frozen suspension, at about 10 ⁇ m in thickness. Sections are mounted on room temperature glass microscope slides, where they will instantaneously melt and adhere. After the sections are air-dried at room temperature, they are coated with gold by sputter coating and observed and photographed using a scanning electron microscope (SEM) (such as the JEOL SEM model JSM-6400, available from JEOL Ltd, Tokyo, Japan).
SEM scanning electron microscope
the shell thickness of 30 encapsulated benefit agents is measured, by selecting 10 encapsulated benefit agents in each of 3 different diameter size fractions.
the 3 different diameter size fractions are determined by the 5 th , 50 th and 95 th percentile values calculated from the diameter datapoints, as measured under method (1) above.
the 3 diameter size fractions are defined (in micrometers) as being: the 5 th percentile value+/ ⁇ 10% of its value; the 50 th percentile value+/ ⁇ 10% of its value; and the 95 th percentile value+/ ⁇ 10% of its value.
the shell thickness is measured at least at 4 different locations spaced equi-distantly around each shell's circumference, i.e., at 0°, 90°, 180° and 270°, yielding 120 thickness measurements in total.
the mean shell thickness (S) of each capsule is calculated using the at least 4 shell thickness measurements for the respective capsule.
This example illustrates encapsulation of an active embedded within secondary compartments to achieve control of the release profile.
a perfume is encapsulated as an illustrative example.
Perfume is often a mixture of polar and non-polar components (e.g. fragrant essential oils or aroma compounds).
polar and non-polar components e.g. fragrant essential oils or aroma compounds.
This example presents a method to encapsulate pre-emulsified perfume in hydrophobic polymer shells, achieving high loading efficiencies, e.g., over 50%.
to first form double emulsions water-in-oil-in-water
three phases were injected into a microcapillary device: 10% PVA (polyvinyl alcohol) in aqueous phase as the continuous phase, ethoxylated trimethylolpropane triacrylate (ETPTA) with a photoinitiator (1%) as the middle phase, and pre-emulsified perfume as an inner phase. See FIG. 1A .
the pre-emulsified perfume was prepared by simple mixing of perfume and surfactant solution. To ensure long-term stability of pre-emulsified perfume, two kinds of surfactants were used, Tween 80 (15.2) and polyvinyl alcohol (PVA), with different hydrophilic lipophilic balances (HLB). For example, in some experiments, pre-emulsified perfume used as an inner phase included 50% perfume, 2.5% PVA, 1% Tween 20 and 46.5% water (all percentages are by weight).
FIG. 1B shows that double emulsions were uniformly formed under jetting conditions, and these droplets were collected in a vial.
the double emulsions were exposed to UV light, forming polymer shells containing pre-emulsified perfume ( FIGS. 1C and 1D ).
the perfume was stained with Nile Red as a tracer.
high loading efficiencies e.g., greater than about 50%
an antioxidant was encapsulated as another illustrative example. See FIG. 2 .
⁇ -pinene encapsulated ETPTA microcapsules were prepared with and without a hydrogel network continuous phase in the microcapsules. These microcapsules were rinsed with DI water the continuous aqueous phase carrying the microcapsules was removed. Upon removal of the surrounding water, drastic difference in microcapsule morphology were observed over time. The aqueous phase of fragrance emulsion is replaced by air as the water evaporates for the control microcapsule. No apparent difference is observed for the PEG hydrogel microcapsule. A uniform hydrogel network in PEG hydrogel microcapsule was observed upon breakage. As shown in FIG. 5 , the control microcapsules have a dispersed phase retention fraction of less than about 40% w/w after 5 days while the hydrogel continuous phase microcapsules have a dispersed phase retention fraction of about 50% w/w.
consumer products include, but are not limited to, products for treating hair (human, dog, and/or cat), including, bleaching, coloring, dyeing, conditioning, shampooing, styling; deodorants and antiperspirants; personal cleansing; cosmetics; skin care including application of creams, lotions, and other topically applied products for consumer use including fine fragrances; and shaving products, products for treating fabrics, hard surfaces and any other surfaces in the area of fabric and home care, including: air care including air fresheners and scent delivery systems, car care, dishwashing, fabric conditioning (including softening and/or freshening), laundry detergency, laundry and rinse additive and/or care, hard surface cleaning and/or treatment including floor and toilet bowl cleaners and cleaning implements, granular or powder-form all-purpose or “heavy-duty” washing agents, especially cleaning detergents; liquid, gel or paste-form all-purpose washing agents, especially the so-called heavy-duty liquid types; liquid fine-fabric detergents;
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.
the phrase “at least one,” in reference to a list of one or more elements, should be understood to mean at least one element selected from any one or more of the elements in the list of elements, but not necessarily including at least one of each and every element specifically listed within the list of elements and not excluding any combinations of elements in the list of elements.
This definition also allows that elements may optionally be present other than the elements specifically identified within the list of elements to which the phrase “at least one” refers, whether related or unrelated to those elements specifically identified.
“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.

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Organic Chemistry (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Birds (AREA)
Dispersion Chemistry (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Wood Science & Technology (AREA)
Oil, Petroleum & Natural Gas (AREA)
Materials Engineering (AREA)
Manufacturing Of Micro-Capsules (AREA)
Cosmetics (AREA)
Fats And Perfumes (AREA)
Medicinal Preparation (AREA)
Detergent Compositions (AREA)
Disinfection, Sterilisation Or Deodorisation Of Air (AREA)

US14/945,479 2014-11-24 2015-11-19 Systems for Encapsulation of Actives within Droplets and other Compartments Abandoned US20160144329A1 (en)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
US14/945,479 US20160144329A1 (en)	2014-11-24	2015-11-19	Systems for Encapsulation of Actives within Droplets and other Compartments

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US201462083729P	2014-11-24	2014-11-24
US14/945,479 US20160144329A1 (en)	2014-11-24	2015-11-19	Systems for Encapsulation of Actives within Droplets and other Compartments

Publications (1)

Publication Number	Publication Date
US20160144329A1 true US20160144329A1 (en)	2016-05-26

Family

ID=54782825

Family Applications (5)

Application Number	Title	Priority Date	Filing Date
US14/945,475 Expired - Fee Related US9718044B2 (en)	2014-11-24	2015-11-19	Compositions comprising encapsulated actives within droplets and other compartments
US14/945,484 Expired - Fee Related US9878299B2 (en)	2014-11-24	2015-11-19	Methods for encapsulation of actives within droplets and other compartments
US14/945,479 Abandoned US20160144329A1 (en)	2014-11-24	2015-11-19	Systems for Encapsulation of Actives within Droplets and other Compartments
US15/635,340 Expired - Fee Related US10434485B2 (en)	2014-11-24	2017-06-28	Compositions comprising encapsulated actives within droplets and other compartments
US16/524,223 Abandoned US20190344237A1 (en)	2014-11-24	2019-07-29	Compositions Comprising Encapsulated Actives within Droplets and other Compartments

Family Applications Before (2)

Application Number	Title	Priority Date	Filing Date
US14/945,475 Expired - Fee Related US9718044B2 (en)	2014-11-24	2015-11-19	Compositions comprising encapsulated actives within droplets and other compartments
US14/945,484 Expired - Fee Related US9878299B2 (en)	2014-11-24	2015-11-19	Methods for encapsulation of actives within droplets and other compartments

Family Applications After (2)

Application Number	Title	Priority Date	Filing Date
US15/635,340 Expired - Fee Related US10434485B2 (en)	2014-11-24	2017-06-28	Compositions comprising encapsulated actives within droplets and other compartments
US16/524,223 Abandoned US20190344237A1 (en)	2014-11-24	2019-07-29	Compositions Comprising Encapsulated Actives within Droplets and other Compartments

Country Status (8)

Country	Link
US (5)	US9718044B2 (fr)
EP (3)	EP3223935A1 (fr)
JP (3)	JP2017537900A (fr)
CN (3)	CN106999361B (fr)
BR (3)	BR112017010819A2 (fr)
CA (3)	CA2966941A1 (fr)
RU (1)	RU2017114553A (fr)
WO (4)	WO2016085740A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2018172433A1 (fr) *	2017-03-21	2018-09-27	Calyxia	Procédé de préparation de capsules comprenant au moins un composé volatile et capsules obtenues
WO2018172360A1 (fr) *	2017-03-21	2018-09-27	Calyxia	Procédé de préparation de capsules comprenant au moins une substance hydrosoluble ou hydrophile et capsules obtenues
US10195571B2 (en)	2011-07-06	2019-02-05	President And Fellows Of Harvard College	Multiple emulsions and techniques for the formation of multiple emulsions
WO2019110590A1 (fr) *	2017-12-06	2019-06-13	Samplix Aps	Dispositif microfluidique et procédé de fourniture de gouttelettes d'émulsion double
KR20190127878A (ko) *	2017-03-21	2019-11-13	칼릭시아	개선된 체류 특성을 갖는 캡슐을 제조하는 방법 및 그로부터 수득된 캡슐

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2010033200A2 (fr)	2008-09-19	2010-03-25	President And Fellows Of Harvard College	Création de bibliothèques de gouttelettes et d'espèces apparentées
EP3065712A4 (fr)	2013-11-08	2017-06-21	President and Fellows of Harvard College	Microparticules, procédés pour leur préparation et leur utilisation
EP3223935A1 (fr) *	2014-11-24	2017-10-04	The Procter and Gamble Company	Systèmes pour l'encapsulation d'agents actifs dans des gouttelettes et autres compartiments
CA3001679A1 (fr)	2015-10-13	2017-04-20	President And Fellows Of Harvard College	Systemes et procedes de fabrication et d'utilisation de microspheres de gel
JP6706774B2 (ja) *	2015-10-23	2020-06-10	国立大学法人東京大学	コアシェル粒子の製造方法
WO2018148485A1 (fr) *	2017-02-09	2018-08-16	Knowles Electronics, Llc	Membrane de récepteur acoustique, combinaisons associées et procédés associés
FR3066116B1 (fr)	2017-05-15	2020-02-14	Calyxia	Procede de preparation de capsules biodegradables et capsules obtenues
US10544413B2 (en)	2017-05-18	2020-01-28	10X Genomics, Inc.	Methods and systems for sorting droplets and beads
EP4435113B1 (fr)	2017-05-18	2025-12-10	10X Genomics, Inc.	Procédés et systèmes de tri de gouttelettes et de billes
US20200197894A1 (en) *	2017-08-21	2020-06-25	President And Fellow Of Harvard College	Poly(acid) microcapsules and related methods
US10821442B2 (en)	2017-08-22	2020-11-03	10X Genomics, Inc.	Devices, systems, and kits for forming droplets
US10544039B2 (en) *	2017-09-08	2020-01-28	Texas Instruments Incorporated	Methods for depositing a measured amount of a species in a sealed cavity
WO2019083852A1 (fr)	2017-10-26	2019-05-02	10X Genomics, Inc.	Réseaux de canaux microfluidiques pour partitionnement
CN108159976A (zh) *	2018-01-03	2018-06-15	西南交通大学	一种油包水包水（w/w/o）单分散双重乳液制备方法及其微流控装置
EP3736297B1 (fr)	2018-01-05	2024-10-16	Toppan Printing Co., Ltd.	Particules composites, procédé de production de particules composites, poudre sèche et composition de résine pour moulage
DE102018200518B4 (de) *	2018-01-15	2023-09-14	Robert Bosch Gmbh	Mikrofluidischen Vorrichtung und Verfahren zu dessen Betrieb
JP2021088612A (ja) *	2018-03-23	2021-06-10	富士フイルム株式会社	マイクロカプセル含有組成物
WO2019208801A1 (fr)	2018-04-27	2019-10-31	凸版印刷株式会社	Particules composites à libération prolongée, procédé de production de particules composites à libération prolongée, poudre sèche et papier peint
WO2019213075A1 (fr) *	2018-04-30	2019-11-07	The Trustees Of Columbia University In The City Of New York	Procédés, systèmes, et appareils pour l'encapsulation d'un milieu de séquestration
US11964294B2 (en) *	2018-07-10	2024-04-23	Panasonic Intellectual Property Management Co., Ltd.	Mist-generating device
CN109126652A (zh) *	2018-09-19	2019-01-04	苏州科技大学	一种自修复微胶囊的微流控制备装置及其制备方法和应用
CN113227250B (zh) *	2018-10-04	2024-01-30	亚历山德拉·乌尼诺夫	无聚氯乙烯的芳香的基于亲脂的聚合物的塑料溶胶
CN109680511B (zh) *	2018-12-04	2021-09-14	浙江理工大学	一种用于商标织物涂层的芳香微胶囊的制备方法
KR102425901B1 (ko) *	2019-05-02	2022-07-28	숙명여자대학교산학협력단	액적화된 하이드로겔 및 이의 제조방법
CN110694704B (zh) *	2019-09-26	2021-10-12	安徽省昂普拓迈生物科技有限责任公司	一种便携式快速微液滴发生器
CN111146429B (zh) *	2020-01-10	2021-03-16	安徽师范大学	一种氧化石墨烯/硫微胶囊复合材料的制备方法、锂硫电池正极、锂硫电池
CN112112640A (zh) *	2020-09-22	2020-12-22	权冉(银川)科技有限公司	一种环保型示踪剂控释胶囊及其方法
KR102648911B1 (ko) *	2021-11-12	2024-03-20	충남대학교산학협력단	캡슐 제조방법 및 캡슐 제조장치

Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20130183375A1 (en) *	2010-04-09	2013-07-18	Pacira Pharmaceuticals, Inc.	Method for formulating large diameter synthetic membrane vesicles

Family Cites Families (46)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS5822062A (ja) *	1981-08-03	1983-02-09	森下仁丹株式会社	高融点物質充填微小カプセルの製造方法及び装置
DE19646880A1 (de)	1996-11-13	1998-05-14	Hoechst Schering Agrevo Gmbh	Endosulfan-Mikrokapseldispersion
DE69813254T2 (de)	1997-08-05	2004-04-01	Microfluidics International Corp., Newton	Hochdruck mischer-reaktor mit mehrfachströmen
JP4208208B2 (ja) *	1998-05-29	2009-01-14	花王株式会社	カプセル粒子の製造方法
JP2000189786A (ja) *	1998-12-24	2000-07-11	Kao Corp	継目無しカプセルの製造装置
US6365189B1 (en) *	1999-10-22	2002-04-02	3M Innovative Properties Company	Method of delivering and releasing a pheromone
US6887493B2 (en) *	2000-10-25	2005-05-03	Adi Shefer	Multi component controlled release system for oral care, food products, nutraceutical, and beverages
US6294457B1 (en)	2001-02-01	2001-09-25	Taiwan Semiconductor Manufacturing Company	Optimized IMD scheme for using organic low-k material as IMD layer
JP4193561B2 (ja) *	2002-04-25	2008-12-10	東ソー株式会社	微小流路構造体、これを用いた微小粒子製造方法及び微小流路構造体による溶媒抽出方法
JP2006507921A (ja)	2002-06-28	2006-03-09	プレジデント・アンド・フェロウズ・オブ・ハーバード・カレッジ	流体分散のための方法および装置
JP2004154745A (ja) *	2002-09-10	2004-06-03	Tosoh Corp	液滴生成用微小流路構造体、これを用いた液滴生成方法及びその生成物
US7670627B2 (en) *	2002-12-09	2010-03-02	Salvona Ip Llc	pH triggered targeted controlled release systems for the delivery of pharmaceutical active ingredients
WO2004091763A2 (fr)	2003-04-10	2004-10-28	President And Fellows Of Harvard College	Formation et regulation d'especes fluidiques
EP2662136A3 (fr)	2003-08-27	2013-12-25	President and Fellows of Harvard College	Méthode de manipulation et de mélange de gouttelettes
US20050226900A1 (en)	2004-04-13	2005-10-13	Winton Brooks Clint D	Skin and hair treatment composition and process for using same resulting in controllably-releasable fragrance and/or malodour counteractant evolution
US20050282011A1 (en) *	2004-06-21	2005-12-22	Nissin Chemical Industry Co., Ltd.	Microcapsule emulsion and method for producing the same
EP1861194A2 (fr) *	2005-03-04	2007-12-05	The President and Fellows of Harvard College	Procede et dispositif permettant de former des emulsions multiples
US7622132B2 (en) *	2005-06-27	2009-11-24	Elc Management, Llc	Encapsulated cosmetic composition
DE102005031467A1 (de)	2005-07-04	2007-01-25	Basf Ag	Emulgatorsystem, Emulsion und deren Verwendung
EP2026771B1 (fr) *	2006-01-23	2009-10-21	Yissum Research Development Company Of The Hebrew University Of Jerusalem	Microsphère comprenant des nanocapsules contenant une substance active lipophile
US7776927B2 (en)	2007-03-28	2010-08-17	President And Fellows Of Harvard College	Emulsions and techniques for formation
US20090155586A1 (en)	2007-12-12	2009-06-18	Avon Products, Inc.	Method of Improving Skin Appearance Using Treated Macroscopic Particles
GB0803538D0 (en) *	2008-02-27	2008-04-02	Dow Corning	Deposition of lipophilic active material in surfactant containing compositions
US8802027B2 (en)	2008-03-28	2014-08-12	President And Fellows Of Harvard College	Surfaces, including microfluidic channels, with controlled wetting properties
US8187554B2 (en)	2008-04-23	2012-05-29	Microfluidics International Corporation	Apparatus and methods for nanoparticle generation and process intensification of transport and reaction systems
US20110305761A1 (en)	2008-06-05	2011-12-15	President And Fellows Of Harvard College	Polymersomes, colloidosomes, liposomes, and other species associated with fluidic droplets
WO2010021307A1 (fr)	2008-08-19	2010-02-25	エドワーズ株式会社	Pompe à vide
BRPI0922486B1 (pt) *	2008-12-18	2017-03-14	Firmenich & Cie	microcápsulas e suas respectivas utilizações
CA2991390A1 (fr)	2009-02-09	2010-08-12	Cellutech Ab	Coques celluloses
BRPI1008965B1 (pt)	2009-03-13	2018-12-18	Harvard College	método para aumento de escala de dispositivos microfluídicos e sistema para a formação de gotículas em canais microfluídicos em paralelo
WO2010104604A1 (fr)	2009-03-13	2010-09-16	President And Fellows Of Harvard College	Procédé destiné à la création contrôlée d'émulsions, comprenant des émulsions multiples
US20120199226A1 (en)	2009-09-02	2012-08-09	Basf Se	Multiple emulsions created using junctions
EP2473263B1 (fr)	2009-09-02	2022-11-02	President and Fellows of Harvard College	Multiples émulsions créées par éjection et autres techniques
US8715544B2 (en)	2009-12-21	2014-05-06	Appvion, Inc.	Hydrophilic liquid encapsulates
KR20130016284A (ko)	2010-03-17	2013-02-14	바스프 에스이	용융 유화
EP2549986B1 (fr) *	2010-03-24	2019-10-30	Northeastern University	Administration multicompartimentale de macrophages
US9192548B2 (en) *	2010-06-25	2015-11-24	CoLabs International Corporation	Ceramic encapsulation with controlled layering by use of functionalized silanes
CN102475691B (zh) *	2010-11-30	2014-04-16	中国科学院大连化学物理研究所	海藻酸盐-壳聚糖酰基衍生物微胶囊及其制备和应用
WO2012162296A2 (fr)	2011-05-23	2012-11-29	President And Fellows Of Harvard College	Génération d'émulsions et, notamment, d'émulsions multiples
WO2013006661A2 (fr) *	2011-07-06	2013-01-10	President And Fellows Of Harvard College	Émulsions multiples et techniques de formation d'émulsions multiples
EP2750787A2 (fr)	2011-08-30	2014-07-09	President and Fellows of Harvard College	Systèmes et procédés d'encapsulation dans des coques
CA2849378A1 (fr) *	2011-09-21	2013-03-28	Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd.	Systemes de nanoliberation pour arnsi
US9956160B2 (en)	2013-03-15	2018-05-01	LeChat	Gel polish thinner
EP2806018A1 (fr)	2013-05-20	2014-11-26	The Procter & Gamble Company	Produits encapsulés
US9598313B2 (en)	2014-05-29	2017-03-21	Nano And Advanced Materials Institute Limited	Self-healing material and preparation process thereof
EP3223935A1 (fr) *	2014-11-24	2017-10-04	The Procter and Gamble Company	Systèmes pour l'encapsulation d'agents actifs dans des gouttelettes et autres compartiments

2015
- 2015-11-19 EP EP15816274.3A patent/EP3223935A1/fr not_active Withdrawn
- 2015-11-19 BR BR112017010819A patent/BR112017010819A2/pt not_active Application Discontinuation
- 2015-11-19 WO PCT/US2015/061482 patent/WO2016085740A1/fr not_active Ceased
- 2015-11-19 CN CN201580063638.2A patent/CN106999361B/zh not_active Expired - Fee Related
- 2015-11-19 BR BR112017010817A patent/BR112017010817A2/pt not_active Application Discontinuation
- 2015-11-19 EP EP15813157.3A patent/EP3223801A1/fr not_active Withdrawn
- 2015-11-19 RU RU2017114553A patent/RU2017114553A/ru unknown
- 2015-11-19 JP JP2017526633A patent/JP2017537900A/ja active Pending
- 2015-11-19 CN CN201580063915.XA patent/CN106999893B/zh not_active Expired - Fee Related
- 2015-11-19 BR BR112017010818A patent/BR112017010818A2/pt not_active Application Discontinuation
- 2015-11-19 CA CA2966941A patent/CA2966941A1/fr not_active Abandoned
- 2015-11-19 US US14/945,475 patent/US9718044B2/en not_active Expired - Fee Related
- 2015-11-19 JP JP2017526642A patent/JP2017537901A/ja active Pending
- 2015-11-19 CA CA2966915A patent/CA2966915A1/fr not_active Abandoned
- 2015-11-19 WO PCT/US2015/061492 patent/WO2016085743A1/fr not_active Ceased
- 2015-11-19 CA CA2966914A patent/CA2966914A1/fr not_active Abandoned
- 2015-11-19 US US14/945,484 patent/US9878299B2/en not_active Expired - Fee Related
- 2015-11-19 CN CN201580063771.8A patent/CN106999892A/zh active Pending
- 2015-11-19 JP JP2017526632A patent/JP2017537776A/ja active Pending
- 2015-11-19 US US14/945,479 patent/US20160144329A1/en not_active Abandoned
- 2015-11-19 EP EP15805025.2A patent/EP3223800A1/fr not_active Withdrawn
- 2015-11-19 WO PCT/US2015/061484 patent/WO2016085741A1/fr not_active Ceased
- 2015-11-19 WO PCT/US2015/061485 patent/WO2016085742A1/fr not_active Ceased
2017
- 2017-06-28 US US15/635,340 patent/US10434485B2/en not_active Expired - Fee Related
2019
- 2019-07-29 US US16/524,223 patent/US20190344237A1/en not_active Abandoned

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20130183375A1 (en) *	2010-04-09	2013-07-18	Pacira Pharmaceuticals, Inc.	Method for formulating large diameter synthetic membrane vesicles

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US10195571B2 (en)	2011-07-06	2019-02-05	President And Fellows Of Harvard College	Multiple emulsions and techniques for the formation of multiple emulsions
KR102525477B1 (ko)	2017-03-21	2023-04-26	칼릭시아	개선된 체류 특성을 갖는 캡슐을 제조하는 방법 및 그로부터 수득된 캡슐
CN110831693A (zh) *	2017-03-21	2020-02-21	卡莉西亚公司	制备包含至少一种挥发性化合物的胶囊的方法和由该方法得到的胶囊
FR3064191A1 (fr) *	2017-03-21	2018-09-28	Calyxia	Procede de preparation de capsules comprenant au moins une substance hydrosoluble ou hydrophile et capsules obtenues
KR20190132432A (ko) *	2017-03-21	2019-11-27	칼릭시아	하나 이상의 수-용해성 또는 친수성 물질을 포함하는 캡슐을 제조하는 방법 및 그로부터 수득된 캡슐
US12186723B2 (en)	2017-03-21	2025-01-07	Calyxia	Method for preparing capsules comprising at least one volatile compound and capsules obtained therefrom
KR20190127881A (ko) *	2017-03-21	2019-11-13	칼릭시아	하나 이상의 휘발성 화합물을 포함하는 캡슐을 제조하는 방법 및 이로부터 수득된 캡슐
KR20190127878A (ko) *	2017-03-21	2019-11-13	칼릭시아	개선된 체류 특성을 갖는 캡슐을 제조하는 방법 및 그로부터 수득된 캡슐
CN110461462A (zh) *	2017-03-21	2019-11-15	卡莉西亚公司	制备具有改善的滞留性能的胶囊的方法和由该方法得到的胶囊
FR3064192A1 (fr) *	2017-03-21	2018-09-28	Calyxia	Procede de preparation de capsules comprenant au moins un compose volatile et capsules obtenues
CN110475607A (zh) *	2017-03-21	2019-11-19	卡莉西亚公司	制备含至少一种水溶性或亲水性物质的胶囊的方法以及由该方法得到的胶囊
WO2018172360A1 (fr) *	2017-03-21	2018-09-27	Calyxia	Procédé de préparation de capsules comprenant au moins une substance hydrosoluble ou hydrophile et capsules obtenues
JP2020511518A (ja) *	2017-03-21	2020-04-16	カリシア	少なくとも１種の水溶性もしくは親水性物質を含むカプセルを製造する方法およびその方法から得られるカプセル
US11071962B2 (en)	2017-03-21	2021-07-27	Calyxia	Method for preparing capsules comprising at least one water-soluble or hydrophilic substance and capsules obtained therefrom
JP7169289B2 (ja)	2017-03-21	2022-11-10	カリシア	少なくとも１種の水溶性もしくは親水性物質を含むカプセルを製造する方法およびその方法から得られるカプセル
WO2018172433A1 (fr) *	2017-03-21	2018-09-27	Calyxia	Procédé de préparation de capsules comprenant au moins un composé volatile et capsules obtenues
KR102528482B1 (ko) *	2017-03-21	2023-05-03	칼릭시아	하나 이상의 휘발성 화합물을 포함하는 캡슐을 제조하는 방법 및 이로부터 수득된 캡슐
KR102534796B1 (ko) *	2017-03-21	2023-05-19	칼릭시아	하나 이상의 수-용해성 또는 친수성 물질을 포함하는 캡슐을 제조하는 방법 및 그로부터 수득된 캡슐
US11779923B2 (en) *	2017-12-06	2023-10-10	Samplix Aps	Microfluidic device and a method for provision of double emulsion droplets
WO2019110590A1 (fr) *	2017-12-06	2019-06-13	Samplix Aps	Dispositif microfluidique et procédé de fourniture de gouttelettes d'émulsion double

Also Published As

Publication number	Publication date
CA2966941A1 (fr)	2016-06-02
CN106999893B (zh)	2020-07-14
CN106999892A (zh)	2017-08-01
CN106999361B (zh)	2019-12-24
CA2966915A1 (fr)	2016-06-02
BR112017010817A2 (pt)	2018-01-09
RU2017114553A3 (fr)	2018-12-26
US9718044B2 (en)	2017-08-01
CA2966914A1 (fr)	2016-06-02
US20160144330A1 (en)	2016-05-26
US10434485B2 (en)	2019-10-08
JP2017537901A (ja)	2017-12-21
WO2016085740A1 (fr)	2016-06-02
EP3223800A1 (fr)	2017-10-04
US20190344237A1 (en)	2019-11-14
WO2016085741A1 (fr)	2016-06-02
CN106999361A (zh)	2017-08-01
US9878299B2 (en)	2018-01-30
RU2017114553A (ru)	2018-12-26
JP2017537900A (ja)	2017-12-21
WO2016085742A1 (fr)	2016-06-02
CN106999893A (zh)	2017-08-01
BR112017010819A2 (pt)	2018-04-03
US20170296996A1 (en)	2017-10-19
EP3223935A1 (fr)	2017-10-04
EP3223801A1 (fr)	2017-10-04
JP2017537776A (ja)	2017-12-21
WO2016085743A1 (fr)	2016-06-02
US20160145535A1 (en)	2016-05-26
BR112017010818A2 (pt)	2018-01-09

Publication	Publication Date	Title
US10434485B2 (en)	2019-10-08	Compositions comprising encapsulated actives within droplets and other compartments
ES2919933T3 (es)	2022-07-29	Microcápsulas producidas a partir de precursores de sol-gel combinados y método de producción de las mismas
US20170319443A1 (en)	2017-11-09	Multiple emulsions comprising rigidified portions
TWI656208B (zh)	2019-04-11	內包香料之膠囊及調配有該膠囊之化妝料
JP2013525087A (ja)	2013-06-20	融解乳化
JP2010089089A (ja)	2010-04-22	マイクロカプセル及びその製造方法
Acevedo et al.	2020	3D nanoprinted liquid-core-shell microparticles
US20200078758A1 (en)	2020-03-12	Methods and Systems for Forming Microcapsules
US20200078757A1 (en)	2020-03-12	Methods and Systems for Forming Microcapsules
JP6793645B2 (ja)	2020-12-02	香料組成物
EP4120991A1 (fr)	2023-01-25	Produit de consommation comprenant une pluralité de microcapsules définies par la surface totale moyenne
US20200078759A1 (en)	2020-03-12	Methods and Systems for Forming Microcapsules
Nawar	2019	Microfluidic Production of Double Emulsions: Designer Microcapsules, Dropmaker Wettability Patterning, and Parallelization

Legal Events

Date	Code	Title	Description
2016-06-14	AS	Assignment	Owner name: PRESIDENT AND FELLOWS OF HARWARD COLLEGE, MASSACHU Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WESNER, JOHN CHRISTOPHER;CAGGIONI, MARCO;ZHU, TAOTAO;AND OTHERS;SIGNING DATES FROM 20151120 TO 20160426;REEL/FRAME:038905/0648 Owner name: THE PROCTER & GAMBLE COMPANY, OHIO Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WESNER, JOHN CHRISTOPHER;CAGGIONI, MARCO;ZHU, TAOTAO;AND OTHERS;SIGNING DATES FROM 20151120 TO 20160426;REEL/FRAME:038905/0648
2018-02-20	STCB	Information on status: application discontinuation	Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION

Date

Code

Title

Description

2016-06-14

Assignment

Owner name: PRESIDENT AND FELLOWS OF HARWARD COLLEGE, MASSACHU

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:WESNER, JOHN CHRISTOPHER;CAGGIONI, MARCO;ZHU, TAOTAO;AND OTHERS;SIGNING DATES FROM 20151120 TO 20160426;REEL/FRAME:038905/0648

Owner name: THE PROCTER & GAMBLE COMPANY, OHIO