Non-Spherical Particles, the Controlled Synthesis of Collections of Same, and Uses of Same

Cross-Reference to Related Applications

[0001] This application claims the benefit of U.S. Provisional Patent Application No. 60/858,149, filed November 10, 2006 and entitled "Non-Spherical Particles, the Controlled Synthesis of Collections of Same, and Uses of Same," the entire contents of which are incorporated herein by reference.

Statement Regarding Federally Sponsored Research

[0002] This work was supported by the NSF (DMR-0602684) and the Harvard MRSEC (DMR-0213805).

Background

Field of the Invention

[0003] This invention generally relates to non-spherical particles, the controlled synthesis of same, and uses of same.

Discussion of Related Art

[0004] In the field of colloid science, there is growing interest in the synthesis of non-spherical, or anisotropic, particles. Particles may be anisotropic, for example, in shape, composition, and/or surface chemistry. The physical properties of non-spherical particles differ from those of spheres. This makes them desirable for controlling light scattering and fluid properties, e.g., suspension rheology, and for engineering biomaterials and colloid structures, e.g., colloid composites. Sophisticated techniques are being developed to create non-spherical particles, but they generally produce relatively small yields, severely limiting their utility for commercial applications. One technique is clusterization, in which droplets of volatile oil and microspheres are dried, producing non-spherical arrangements of microspheres. Another technique is stamping.

in which particles are attached electrostatically to each other on a surface, forming "snowman'Mike particles. In microfluidic techniques, deformed droplets are hardened within microchannels using UV light. The particle sizes and shapes can be tuned by changing flow properties. In controlled nucleation and precipitation techniques, the nucleation of inorganic particles is controlled to fonn shapes such as rods, disks, and cubes. For further details on applications of and methods of making non-spherical particles, please refer to the incorporated literature references, which are incorporated in their entirety by reference.

[0005] It is important to develop methods for fine-tuning the geometry and chemical compositions of anisotropic particles. Moreover, to make these particles practical for use in commercial applications, they should be produced in bulk rather than a particle- by-particle basis.

Summary

[0006] A flexible synthetic approach for the controlled, uniform, large-scale synthesis of a variety of non-spherical particle types, collections of non-spherical particles, and uses of same are provided.

[0007] Under one aspect, a collection of particles includes at least about 60% non- spherical particles, each of the non-spherical particles including a first spheroid having a first polymer composition; a second spheroid having a second polymer composition; and a third spheroid having a third polymer composition. The first and second polymer compositions at least partially interpenetrate at a juncture of the first and second spheroids, and the third polymer composition at least partially interpenetrates at least one of the first and second polymer compositions at a juncture of the third spheroid with at least one of the first and second spheroids.

[0008] Some embodiments include one or more of the following features. The collection includes at least about 70% of the non-spherical particles. The collection includes at least about 80% of the non-spherical particles. The collection includes at

least about 90% of the non-spherical particles. The collection includes at least about 95% of the non-spherical particles. The collection includes at least about 99% of the non-spherical particles. The first, second, and third spheroids each have a defined portion of their surface area that is substantially spherical. The non-spherical particles are chemically anisotropic. The non-spherical particles are amphiphilic. At least one of the first, second, and third spheroids further includes a functionalized surface. The first polymer composition includes at least one polymer that is different from at least one of the second and third polymer compositions. The first polymer composition has a cross- linking density that is different from a cross-linking density of at least one of the second and third polymer compositions. Each of the non-spherical particles is generally shaped like a rod, a cone, a snowman, or a triangle. At least one of the first, second, and third spheroids is larger than at least one other of the first, second, and third spheroids. At least one of the first, second, and third polymer compositions includes at least one of polystyrene, methyl acrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, butyl methacrylate, pentyl acrylate, pentyl methacrylate, glycidyl methacrylate, 3- (trimethoxysilyl)-propyl acrylate, 2-hydroxy ethyl methacrylate, acrylic acid, methacrylic acid, boromostyrene, chlorostyrene, chloromethyl styrene, vinyl silane, vinyl chloride, vinylidene chloride, vinyl acetate, mixtures thereof, and copolymers thereof. The first polymer composition comprises polystyrene, and at least one of the second and third polymer compositions includes one of polystyrene and methylmethacrylate. At least one of the non-spherical particles further includes a fourth spheroid having a fourth polymer composition, wherein the fourth polymer composition at least partially interpenetrates at least one of the first, second, and third polymer compositions at a juncture of the fourth spheroid with at least one of the first, second, and third spheroids.

[0009] Under another aspect, a method of making a non-spherical particle of defined shape includes providing a seed particle including first and second spheroids, the first spheroid having a first polymer composition with a first cross-linking density, and the second spheroid having a second polymer composition with a second cross-

linking density, wherein the first and second polymer compositions at least partially interpenetrate at a junction of the first and second spheroids; swelling the seed particle with a solution including a monomer; and polymerizing the monomer to form a third polymer composition, wherein the third polymer composition phase separates from the first and second polymer compositions to form a third spheroid and the first and second cross-linking densities are selected to define a growth direction of the third spheroid and thus define the shape of the non-spherical particle.

[0010] Some embodiments include one or more of the following features. The third polymer composition phase separates from at least one of the first and second spheroids and forms an interpenetrating polymer juncture of the third spheroid with at least one of the first and second polymer compositions. Selecting the first cross-linking density to be sufficiently higher than the second cross-linking density such that the third spheroid phase separates from the seed particle at the second spheroid. The third spheroid phase separates from a side of the second spheroid opposite the first spheroid. Selecting the first and second cross-linking densities to be sufficiently similar so that the third spheroid phase separates from both of the first and second spheroids. The third spheroid grows substantially perpendicularly from a juncture between the first and second spheroids. Fabricating a collection of the non-spherical particles. Selecting the first and second crosslinking densities such that about 90% of the non-spherical particles have substantially the same shape. Selecting the first and second crosslinking densities such that at least about 95% of the non-spherical particles have substantially the same shape. Selecting the first and second crosslinking densities such that at least about 99% of the non-spherical particles have substantially the same shape. Swelling the seed particles with the monomer includes at least partially penetrating the monomer into at least one of the first and second polymer compositions and uncoiling at least some polymer chains in the at least one of the first and second polymer compositions. Polymerizing the monomer comprises generating an elastic force in at least one of the first and second polymer compositions that at least partially squeezes the monomer out

of the at least one of the first and second polymer compositions. Polymerizing the monomer comprises adding a cross-linking agent to the monomer.

[0011] In some embodiments, providing the seed particle includes providing a particle; swelling the particle with a solution including a second monomer; adding a cross-linking agent to the second monomer in an amount selected to produce the first spheroid having the first polymer composition having the first cross-link density; swelling the first spheroid with a third monomer; and adding a cross-linking agent to the third monomer in an amount selected to produce the second spheroid having the second polymer composition having the second cross-link density, the first and second polymer compositions at least partially interpenetrating at the juncture of the first and second spheroids.

[0012] Under another aspect, a non-spherical chemically anisotropic particle includes a first spheroid having a first polymer composition having a first functional feature at the surface of the first spheroid; and a second spheroid having a second polymer composition, wherein the first polymer composition at least partially interpenetrates the second polymer composition at a juncture of the first spheroid to the second spheroid, and wherein the first functional feature imparts a surface property to the particle. The first and second polymer compositions and the first functional feature can be selected such that the particle is amphiphilic and/or a surfactant. Optionally, the second spheroid may include a second functional feature that, e.g., imparts a surface property to the particle.

[0013] Under another aspect, a method of making a non-spherical chemically anisotropic particle includes providing a seed particle having a first polymer composition with a first cross-linking density and a first plurality of molecules having active sites; reacting the active sites with a second plurality of molecules selected to provide a desired surface property; swelling the seed particle with a monomer; and polymerizing the monomer to foπn a second polymer composition, wherein the first and

second polymer compositions at least partially interpenetrate at a juncture of the first and second spheroids.

[0014] In some embodiments, the first spheroid has a modified surface and the second spheroid substantially does not. In other embodiments, both the first and second spheroids have chemically modified surfaces and the surface modifications are selected to provide, alone or in combination, a predetermined surface property.

[0015] Some embodiments include one or more of the following features. Swelling the seed particle with the monomer includes the monomer at least partially penetrating the first polymer composition and uncoiling at least some polymer chains in the first polymer composition. Polymerizing the monomer includes generating an elastic force in the first polymer composition that at least partially squeezes the monomer out of the first polymer composition. Polymerizing the monomer includes adding a cross-linking a ^• *ge>e ^v nt to the monomer.

[0016] Under another aspect, a colloidosome includes a first liquid; a droplet of a second liquid that is substantially immiscible with the first liquid; and plurality of non- spherical chemically anisotropic particles arranged at an interface between the first liquid and the droplet of the second liquid, each particle including a first spheroid including a first polymer composition and having a surface with a first hydrophilicity and a second spheroid including a second polymer composition and having a surface with a second hydrophilicity, wherein the first polymer composition at least partially inteipenetrates the second polymer composition at a juncture of the first spheroid with the second spheroid, wherein the first and second hydrophilicities are selected such that substantially all of the first spheroids are in the first liquid, and substantially all of the second spheroids are in the second liquid.

[0017] Some embodiments include one or more of the following features. The surface of the first spheroid includes a plurality of functional features. The surface of the second spheroid includes a plurality of functional features. The first and second

spheroids each have sizes selected to provide the colloidosome with a selected radius of curvature.

[0018] Under another aspect, an emulsion includes a first liquid; a plurality of droplets of a second liquid that is substantially immiscible with the first liquid; and plurality of non-spherical chemically anisotropic particles arranged at a plurality of interfaces between the first liquid and the droplet of the second liquid, each particle including a first spheroid comprising a first polymer composition and having a surface with a first hydrophilicity and a second spheroid comprising a second polymer composition and having a surface with a second hydrophilicity, wherein the first polymer composition at least partially interpenetrates the second polymer composition at a juncture of the first spheroid with the second spheroid, wherein the first and second hydrophilicities are selected such that a majority of the first spheroids are in the first liquid, and a majority of the second spheroids are in the second liquid.

[0019] Some embodiments include one or more of the following features. The surface of the first spheroid includes a plurality of functional features. The surface of the second spheroid includes a plurality of functional features. The first and second spheroids each have sizes selected to define an approximate size of the droplets of the second liquid.

Brief Description of the Drawings

[0020] The drawings are intended to be illustrative only, and non-limiting of the invention.

[0021] In the Drawing:

[0022] Fig. IA is a flow chart of a conventional method of making non-spherical dimer particles using seeded polymerization.

[0023] Fig. IB schematically illustrates the swelling and polymerization steps of Fig. IA: spheroid a originates from the seed particle, and spheroid b originates from the newly polymerized phase.

[0024] Figs. 1C, IC-I, and lC-2 illustrate the effect of polymerization on the phase separation of the first and second spheroids during polymerization.

[0025] Fig. ID is an optical microscope (OM) image of polystyrene dimcr particles after polymerization.

[0026] Fig. IE is an OM image of polystyrene/poly(methyl methacrylate) (PS/PMMA) dimer particles.

[0027] Fig. I F is a scanning electron microscope (SEM) image of PS/PMMA dimer particles.

[0028] Fig. IG is an OM image of PS/PMMA dimer particles dispersed in silicone oil.

[0029] Figs. 2A-2C are OM images of intermediate particles formed during a method of making an exemplary dimer particle.

[0030] Figs. 3A-3D are OM images of exemplary non-spherical particles, according to some embodiments.

[0031] Fig. 4 is a flow chart in steps in a method for fabricating trimer particles, according to some embodiments.

[0032] Figs. 5 A and 5B are schematic illustrations of the growth of trimer particles, according to some embodiments.

[0033] Fig. 6 illustrates an experimentally determined relationship between cross- linking density gradient, relative concentrations of cross-linking agent, and non- spherical particle shape, according to some embodiments.

[0034] Fig. 7 A illustrates a time series of optical microscope images recorded with a digital camera during the growth of the third spheroids of trimer particles of two different shapes, according to some embodiments.

[0035] Fig. 7B illustrates changes over time of the relative diameter of the spheroids during the growth of the third spheroids of the trimer particles of Fig. 7 A, according to some embodiments.

[0036] Fig. 8 is a flow chart of steps in a method of fabricating amphiphilic particles, accordin ^L og to some embodiments.

[0037] Fig. 9A is an optical microscope image of asymmetrically phase-separated polystyrene (PS) particles, according to some embodiments.

[0038] Fig. 9B is an optical microscope image of symmetrically phase-separated dimer particles with glycidyl methacrylate (GMA) copolymerized into the cross-linked polystyrene (CPS) particles, according to some embodiments.

[0039] Fig. 9C is an SEM image of amphiphilic PS dimer particles obtained by reacting the epoxy groups of GMA, copolymerized into the CPS particles, with poly (ethylene imine) (PEI), according to some embodiments.

[0040] Fig. 9D is a fluorescence microscope image of dye-labeled amphiphilic PS dimer particles, according to some embodiments.

[0041] Fig. 9E is an optical microscope image of amphiphilic PS dimer particles assembled at water/ 1-octanol interface, according to some embodiments.

[0042] Fig. 10 is a photograph of the results of a simple packing experiment for three different particle shapes, according to some embodiments.

[0043] Fig. 1 1 schematically illustrates the growth of chemically anisotropic particles, according to some embodiments.

[0044] Figs. 12A-12D are images of particles, according to some embodiments.

[0045] Figs. 13A-13C are images of colloidosomes formed with chemically anisotropic particles, according to some embodiments.

Detailed Description

Overview

[0046] Non-spherical particles of predictable shape and composition, the controlled synthesis of same, and uses of same are described. In particular, particles having chemical, compositional, and/or geometric anisotropy are described. Under some aspects, a flexible synthetic approach for fabricating anisotropic non-spherical particles allows control over their phase and surface chemistries, while maintaining their uniformity in shape and size in a collection of particles. The seeded polymerization techniques described herein provide a convenient means to manipulate the geometry and surface properties of non-spherical particles, and to be able to do so uniformly for a large collection of particles. The resulting particles are useful in many applications. For example, particles with chemical anisotropy can play a role in recognizing specific molecules, self-assembling colloids, forming Pickering emulsions, and stabilizing bubbles. One particularly useful example of chemical anisotropy is "amphiphilicity" which would allow the particles to be used in a wide variety of surfactant applications, as discussed in greater detail below.

[0047] The non-spherical particles have two or more distinct bulbs or spheroids of polymer of similar or different composition that are joined or fused together. By "spheroid," it is meant a body that is distorted from a perfect sphere, typically because it is merged or joined with an adjacent spheroidal body. In some embodiments, the minor and major axis of the spheroids may differ, e.g., one axis may be extended or contracted as compared to the other. In some embodiments, approximately 60-90% of one or both of the spheroids may be approximately spherical. At the juncture of two spheroids, the spheroids merge and their polymer networks interpenetrate, joining the spheroids to

each other. The spheroids can be of the same or different size. In its simplest form, the non-spherical particles contain two spheroids ('dimer'), a and b, of similar size and have a 'dumbbell' shape, as illustrated by particle 103' in Figure IB. In other embodiments, the non-spherical particles contain three particles ('trimer'), which can take on a variety of orientations. By way of some non-limiting examples, the trimer may include three spheroids of approximately equal size that are aligned along a single axis for form an extended 'rod' geometry, as is illustrated in Figure 3A. The three spheroids can be alternatively arranged to form a 'triangle' particle, as shown in Figure 3B. Thus, particles having two spheroids are referred to herein as "dimers," and particles having three spheroids are referred to herein as "trimers." Other non-spherical shapes and sizes are contemplated, as is illustrated in further examples described herein.

[0048] The spheroids can have the same polymer composition, or they can be different, depending on the intended use of the non-spherical particle. For example, chemically anisotropic non-spherical particles having two or more spheroids can be made by using different polymer compositions in the different spheroids and/or by chemically modifying the surfaces of one or more of the spheroids, as described in greater detail below. In other embodiments, the spheroids may have similar polymer composition, but differ in crosslink density. In other embodiments, non-spherical particles having three or more spheroids can be formed; the composition of the spheroids can the same or different, and one or more spheroids may include a surface treatment that makes the particles chemically anisotropic. In one embodiment, the non- spheroidal particles can be amphiphilic, e.g., it can possess domains having hydrophilic and hydrophobic properties. Chemically anisotropic, e.g., amphiphilic, non-spherical particles allow a wide range of potential applications, such as colloid surfactants.

[0049] The non-spherical particles are fabricated using seeded polymerization techniques in which the cross-linking densities of seed particles are manipulated in order to control the extent and direction of growth of new spheroids from those seed particles. The seed particles may be approximately spheres, for example, if chemically anisotropic particles having two spheroids are desired, or may themselves be

multispheroidal particles, e.g., dimers or trimers, if particles having three or more spheroids are desired.

[0050] As described in greater detail below, the seed particles are first swollen with a monomer. Next, the monomer-swollen seed particle is polymerized, which induces a phase separation between the polymer making up the seed particle and the polymerizing monomer. Depending on the cross-linking density of the seed particle, the polymerizing monomer phase-separates from the seed particle in a particular location, foπning a new spheroid that is not only adjacent to the seed particle in that location, but whose polymer network interpenetrates with the polymer network of the seed particle. For example, if the seed particle has two spheroids having two different cross-linking densities, the seed particle has an inherent cross-linking density gradient that controls the phase separation and thus direction of growth of the spheroid of newly polymerized monomer. This precise control over phase separation patterns allows novel non-spherical particle shapes to be obtained, and produces sufficient quantities to characterize their bulk properties, for example, their close-packed volume fractions.

[0051] As noted previously, particles having two spheroids are referred to herein as "dimers," and particles having three spheroids are referred to herein as "trimers." Note however that the word "monomer" has its conventional meaning, that is, meaning chemical units that are covalently bound together during polymerization steps to form polymeric compositions.

Controlled Synthesis of Non-Spherical Dimer Particles

[0052] Fig. IA is a schematic of a conventional seeded polymerization technique that can be used to fabricate particles having two "bulbs" or spheroids, i.e., "dimers." First, a plurality of seed particles, e.g., approximately spherical particles having a first polymer composition, are provided (101). Next, the seed particles are swollen with a polymerizable monomer-based solution, which optionally includes a crosslinker (102). Exemplary monomer-based solutions are described in greater detail below, and in the incorporated literature references. The monomer in the solution at least partially

penetrates the seed particles. Then, the monomer is polymerized to foπn a second polymer composition (103), for example, by adding a cross-linking agent to the monomer that causes the monomer to cross-link and thus polymerize. During this polymerization step, the first and second polymers phase separate and the second polymer is expelled or 'grows' from the seed particle, forming first and second spheroids, where the first spheroid corresponds to the seed particle, the second spheroid coiTcsponds to the newly polymerized monomer. Because the phase separation is not complete, the first and second polymer compositions form interpenetrating networks, which joins the first spheroid to the second spheroid.

[0053] Fig. IB schematically illustrates steps in the method of Fig. IA. First, a seed particle is provided (101 '), e.g., having a cross-linked polystyrene composition (CPS). The monomer then swells the seed particle (102'), for example, by soaking the seed particles in a monomer solution under preselected conditions (e.g., >10 hours at room temperature). Next, the first and second spheroids are created during the polymerization step (103'). Without wishing to be bound by theory, it is believed that the polymerization causes an elastic stress that partially squeezes the second polymer phase out of the first polymer to form the second spheroid. Some part of the second polymer composition remains within the first polymer composition, so that the first and second polymer compositions form a partially interpenetrating network (IPN) between two substantially pure regions of phase separated first and second polymer compositions. The size of the second spheroid relative to the first spheroid, and the extent to which the first and second polymer compositions form an IPN, can be controlled by adjusting process parameters, as described below and in the incoiporated literature references. The method can modified to obtain spheres as well as shapes of higher aspect ratio (e.g., ellipsoids) by partially or completely cross-linking the seed particles before the phase separation. Shapes of higher aspect ratio are also compatible with the methods described below, for example, they can be used as seed particles from which other high- aspect ratio shapes or spheroids may be grown using seeded polymerization methods.

However, the discussion below focuses on non-spherical particles with two or more spheroids, i.e., dimers and higher-order particles such as trimers, quadrimers, and larger.

[0054] Figs. 2 A-2C are optical microscope (OM) images of exemplary dimer particles formed using the conventional method described with reference to Figs. IA and IB. Fig. 2A shows cross-linked polystyrene (CPS) seed particles, which are about 2.7 μm in diameter and have a semi-interpenetrating polymer network (IPN) structure (~20 vol% linear PS). "Semi-interpenetrating" means the polymer network structure includes linear polymers and polymer networks. In contrast, "fully-interpenetrating" means a network structure with two different polymer networks. In this example, the crosslinking density, measured for the gel fraction, is about 61 mol-m ^"3 . Fig 2B shows the seed particles after they have been swollen by a solution including styrene monomer, divinylbenzene (DVB, 1 vol% against monomer), and monomer-soluble initiator (V- 65B, 2,2'-azodi(2,4'-dimethyl-valeronitrile)) at room temperature for more than 10 h. The swollen particles are approximately three times the initial volume of the seed particles. Fig. 2C shows the phase-separated dimers formed after heating the swollen seed particles to the polymerization temperature of about 7O ⁰ C for about eight hours to induce the formation and polymerization of the second polymer that forms the second spheroid.

[0055] Figs. 1C, IC-I, and lC-2 illustrate the effect of polymerization on the phase separation of the first and second spheroids during polymerization. Fig. 1C illustrates the relative diameters of the swollen seed particle and the second spheroid as it grows over time, during an illustrative implementation of the above-described method, performed first using the monomer-soluble initiator V-65B, and repeated without the monomer-soluble initiator, allowing the contributions of elastic stress and polymerization to the phase separation of the first and second polymers to be evaluated. In Fig. 1C, squares indicate measurements on particles formed without V-65B initiator, and circles indicate measurements on particles foπned with 0.5 wt% V-65B. The measurements were obtained by directly imaging the particles with a digital camera- equipped optical microscope during the phase separation process. The insets IC-I and

lC-2 are OM images of the phase-separated PS particles (CPS/Styrene = 1/3, weight/volume) prepared by heating at 70 ⁰ C for 3 h without V-65B (IC-I) and with 0.5 wt% V-65B (lC-2), respectively. Even without initiator, on increasing the temperature, the monomer-swollen CPS seed particles phase-separate and form small monomer spheroids that are attached to the CPS particles.

[0056] As Fig. 1C illustrates, when there is no initiator present, there is substantially no growth of the second spheroids after 100 seconds. In contrast, in the presence of initiator, the second spheroids keep growing until substantially all of the monomers are converted to polymers. Without wishing to be bound by theory, this result suggests that the initial phase separation is driven predominantly by the elastic stress induced by simple swelling of the polymer particle; then, as the polymerization proceeds, the phase separation is enhanced due to the difference of free volumes between the seed polymers and newly generating polymers, which eventually results in dimer particles having a rigid dimer shape, as illustrated in Figure ID. Refer to the incorporated literature references for further details on the different theoretical contributions to the characteristics of the particles as they are formed.

[0057] While the conventional fabrication of simple dimers (where both spheroids are based on the same polymer composition, such as polystyrene) using seeded polymerization techniques is known, these fabrication techniques have generally not provided for the controlled and uniform fabrication of more complex structures. For example, previous attempts to fabricate dimers with spheroids of two different polymer compositions, using the method of Fig. IA, have generally resulted in the fabrication of other particle structures, such as "core-shell," "raspberry," "daisy," and "golf-ball" structures, but without significant control over the resulting structure. In many cases, conventional seeded polymerization techniques appear to allow the fabrication of populations containing at most about 50-60% of higher-order particles of a desired shape. For further details, see the incorporated literature references.

[0058] More sophisticated control over the structure of dimers and higher-order particles such as trimers, even with different polymers in each of the different spheroids of the particles, can be achieved by carefully controlling the cross-linking properties of the seed particles. Whereas conventional methods typically used seed particles made of substantially linear polymer compositions, such as linear polystyrene, using seed particles with well-defined cross-linking densities provides a higher degree of control over the phase separation process and hence the shape of the resultant particles. Specifically, defining the cross-linking network of the seed particles adjusts the relative miscibilities of the first polymer composition in the seed particle, the monomer with which the seed particle is swelled, and the second polymer composition formed by polymerizing the monomer. Controlling these miscibilities provides control over the phase separation of the polymers relative to each other, and thus provides excellent control over the shape of the resulting dimer particle. This rationale can be extended to the fabrication of higher-order particles, as discussed in greater detail below.

[0059] For example, when the dimer particles are prepared with CPS seed particles and methyl methacrylate (MMA) monomer instead of styrene, the phase separation during polymerization occurs more readily due to immiscibility between CPS and poly(methyl methacrylate) (PMMA). Fig. IE is an OM image of (PS/PMMA) (CPS/MMA = 1/2, weight/volume) dimer particles, Fig. IF is a scanning electron microscope (SEM) image of the dimer particles, and Fig. IG is an optical microscope image of the dimer particles dispersed in a silicone oil (Dow Coming #550, n = 1.4945), where n is the refractive index. As shown in the optical microscope images of Figs. IE and IF, the particles produced are "dumbbells," i.e., both of the spheroids have approximately the same size. Moreover, as the optical microscope image of Fig. 1 F shows, comparison of the refractive indexes (PS, n = 1.5894; PMMA, n = 1.4893) confirms that the particles include three different phases: linear PS (from the seed particles, ~7 vol%), an interpenetrating network of PS and PMMA, and PMMA. This suggests that, in addition to the elastic effect, the control of polymer-polymer miscibility can play an important role in creating compartmentalized non-spherical particles.

Specifically, the MMA monomer is readily miscible with the PS seed particles. However, when the monomer is polymerized to PMMA, its irascibility in PS is changed, such that it is not completely miscible with PS. Thus, a stronger phase separation can be obtained by using pairs of at least partially immiscible polymers.

[0060] Although the illustrated embodiments use PS and MMA, a variety of polymers can also be used to fabricate similar non-spherical particles, such as acryl monomers, including methyl acrylate, ethyl acrylate, ethyl methacrylate, butyl acrylate, butyl methacrylate, pentyl acrylate, pentyl methacrylate, glycidyl methacrylate, 3- (trimethoxysilyl)-propyl acrylate, 2-hydroxy ethyl methacrylate, acrylic acid, and methacrylic acid; styrene derivatives, including boromostyrene, chlorostyrene, and chloromethyl styrene; vinyl monomers, including vinyl silane, vinyl chloride, vinylidene chloride, and vinyl acetate; and mixtures, such as copolymers, thereof.

Controlled Synthesis of Higher Order Non-Spherical Particles

[0061] "Dimer" particles may be used as seed particles for the controlled synthesis of higher-order non-spherical particles. Figs. 3A-3D are micrographs of a variety of illustrative particle shapes, including "rods," "cones" or "snowmen," "triangles," and "diamonds," that can be fabricated using dimer particles as inteπnediate particles. Fig. 3 A shows an image of an exemplary collection of rods, a schematic illustration of a rod (inset), as well as a more detailed image of a rod. In this example, the diameters of the spheroids in the rods are approximately equal. Fig. 3B shows an image of an exemplary collection of triangles, a schematic illustration of a triangle (inset), as well as a more detailed image of a triangle. In this example, the diameters of the spheroids in the triangles are approximately equal. Fig. 3C shows an image of an exemplary collection of cones/snowmen, a schematic illustration of a cone/snowman (inset), as well as a more detailed image of a cone/snowman. In this example, the diameters of the spheroids within a given cone/snowman are all different sizes, with a larger spheroid on one end, an intermediate size spheroid in the middle, and a smaller spheroid on the other end. Fig. 3D shows an image of an exemplary collection of diamonds, a schematic

illustration of a diamond, as well as a more detailed image of a diamond. In this example, the diameters of the spheroids in the diamonds are approximately equal.

[0062J As described in greater detail below, the particle shapes are related to the cross-linking properties of the first and second spheroids of the dimer seed particles. Thus, by selecting the cross-linking properties of the first and second spheroids during their respective fabrications, the characteristics of more complex particles using the dimers as seed particles may be selected.

[0063] Fig. 4 illustrates a method (400) of fabricating complex particles (trimers or larger) of controlled shape. First, seed particles having a first spheroid a with a first polymer composition and a first crosslinking density v _a , and a second spheroid b with a second polymer composition and having a second crosslinking density v _t , are provided or fabricated (401), for example as described in the incorporated literature references, or as described herein. The second crosslinking density v _/ , may be defined, for example, by using a particular percentage of crosslinking agent when polymerizing the second polymer composition. Next, the dimer seed particles are swollen with a monomer (402). Depending on the respective cross-linking densities v of the first and second spheroids, the monomer may penetrate each spheroid of the dimer seed particle to a greater or lesser extent. As illustrated in Fig. 5 A, if v _a >V _b , then the monomer will swell the second spheroid b more than it will swell the first, a. Or, as illustrated in Fig. 5B, if v _a ~V _b , then the monomer will swell the first and second spheroids a and b comparably. Next, the swollen dimer is polymerized to form a form a third spheroid c having a third polymer composition with a third cross-linking density v _c (403) and thus form a trimer particle having first, second, and third spheroids.

[0064] The crosslinking density gradient between the polymer compositions in spheroids a and b, Av=v _a -V _b determines the direction of growth of the third spheroid c during the polymerization step (403). As illustrated in Fig. 5 A, if v _a >V _b , and the second spheroid was therefore more swollen than the first spheroid during step (402), then during the polymerization step the second spheroid will exert an elastic stress on the

monomer that is greater than that in the first spheroid. Thus, the third spheroid will grow substantially from the second spheroid, away from the first spheroid (404). As illustrated in Fig. 5B, if v _a ~Vb, and the first and second spheroids were comparably swollen during step (403), then during the polymerization step the first and second spheroids will exert comparable elastic stresses on the monomer . The third spheroid will therefore grow substantially perpendicularly to the joint between the first and second spheroids (405). Typically, heating during the polymerization causes the polymer chains in the first and/or second spheroids to contract, thus exerting the elastic stress on the monomer with which the spheroid is swollen.

[0065] Using this rationale, the steps of swelling and polymerizing with a selected crosslinking density can be repeated to fabricate collections of particles, each particle having a desired number of location-controlled spheroids. Each new spheroid that is added to the particle can have the same composition, or can have a different composition than one or more other spheroids, as each spheroid may be added independently of the others. By appropriately selecting the crosslinking densities of the various spheroids, collections of particles can be created in which a large number of the particles have substantially the same shape as one another. In some embodiments, up to about 60%, up to about 70%, up to about 80%, up to about 90%, up to about 95%>, or even up to about 99% of the particles in the collection have substantially the same shape as one another. As mentioned above, conventional methods have generally only achieved collections having about 50-60% particles with the same shape.

[0066] Using the method of Fig. 4, different kinds of exemplary trimers (three- spheroid particles) were fabricated from different types of dimers. First, linear PS template particles were swollen with styrene monomers containing a cross-linker, divinylbenzene (DVB), and then polymerized to fabricate spherical cross-linked polystyrene (PS) particles, having a first cross-linking density (step a). In step a, the concentration of DVB, [DF^] _n , was fixed at 1 vol% relative to the total monomers. The particles were then again swollen with monomer and then polymerized (step b), resulting in substantially symmetrical phase-separated PS dimers. The size and

appearance of the dimers produced were substantially identical for all samples. In step b, [DVB]^ was varied from 0.5 vol% to 1.1 vol%. Finally, the dimers were again swollen with a similar mixture, and polymerized following the same procedure (step c). This resulted in trimer particles of various shapes. The shape of the trimers was found to depend, at least in part, on [DVB\ . High values of [.DPB] ₆ produced triangle particles, intermediate values of [Df ⁷ Sl, produced triple rod particles, and the lowest value of [DFB] ₄ gave rise to snowman particles.

[0067] To understand this behavior, the relationship between [DFB] ₄ and the internal network properties of the dimers is examined. As illustrated in Figs. 5 A and 5B, the material added during step a resides mostly in one of the dimer spheroids, spheroid a. The second spheroid, spheroid b, contains mostly material added in step b. Therefore, the dimers have cross-linking density gradients when [DFB] ₀ ≠ [DFδ|, . The existence of these gradients was confirmed with dimer swelling experiments, in which a few seed dimers were transferred to toluene. Because toluene is a relatively good solvent for PS, it causes the polymer chains to uncoil. Thus, the particles swell until they reach an equilibrium size where the solvency of the polymers is balanced by the elastic stretching of the network. Because the elasticity of the network is proportional to its cross-linking density, it is possible to estimate the cross-linking density from the polymer volume fraction, φ , the ratio of the un-swollen volume to the swollen volume. These principles are formalized by the theory of Flory and Rehner (see the incoiporated literature references), which for a perfect network gives that the cross-linking density v \φ ^Vi where, N _A is Avogadro's number, and F ₁ is the molar volume of the solvent. The polymer-solvent interaction parameter, χ for the cross-linked PS system can be estimated using χ - 0.431 - 0.31 \φ - 0.036^ ² . These relations allow the cross-linking densities, v _a and v _t , of spheroids a and b, to be determined from images of the particles taken before and after swelling.

[0068] Measured values of v _a and v _b showed that when [DVB\ I[DVB\ < 1 , spheroid b is indeed less cross-linked than spheroid a. As [DKB] ₄ /[DPB] ₃ approaches unity, the cross-linking of spheroid b approaches that of spheroid a. This demonstrates that the gradient of cross-linking density, δv=v _a -v _/> of the PS dimers is tunable by changing the relative concentration of DVB added to form each spheroid, as shown in Fig. 6. Fig. 6 is a plot of the cross-linking density gradient δv versus [DFB] ₀ /[DFδ] _a . δv values were obtained by imaging the dimer particles before and after swelling in toluene. The three insets are the dimer particle images before (upper images) and after (lower images) swelling for [DFB] ₄ Z[DFB] ₀ = L l, 0.7, and 0.5. Although the unswollen dimers appear to be identical, their different network properties account for the dramatic increase in subsequent trimer morphology.

[0069J Thus, the morphology of the trimers correlates strongly with δv. In the symmetric case where δv is relatively small, spheroid c grows substantially perpendicularly to the line between spheroid a and spheroid b, finally forming a "triangle" particle, as illustrated in Fig. 5B. When δv is slightly larger (e.g., about 15 mol-m ^"3 ), the placement of spheroid c breaks symmetry and grows linearly adjacent to spheroid b, thus foπning a triple "rod" particle, as illustrated in Fig. 5A. In an inteπnediate regime of δv, a mixture of the two particle types is obtained. For example, at a δv of approximately 10 mol-m ^"3 , triple rods and triangles are produced simultaneously. If δv is too large (e.g., about 37 mol-m ^"3 ), substantially no phase separation occurs in the final step because v _/ , is insufficient for generating the necessary elastic forces. Thus, by tuning the synthesis conditions, populations of particles of a single type can be fabricated with more than about 90%, more than about 95%, or even more than 99% accuracy.

[0070] Fig. 7A illustrates a time series of optical microscope images recorded with a digital camera during the growth of the third spheroids under two different δv conditions, in order to elucidate the underlying physical mechanisms of the different directionalities of growth. The upper set of images shows the growth of a triple rod

particle during the polymerization of a swollen dimer having a δv of about 5.3 mol-m ^"3 . The lower set of images shows the growth of a triangle particle during the polymerization of a swollen dimer having a δv of about 0.9 mol-m ^"3 . The images reveal a remarkable difference in phase separation kinetics: the new spheroids of the triple rods formed within about 48 sec, while the new spheroids of the triangles required approximately 3 h. Fig. 7B illustrates changes over time in the relative diameter of the spheroids during the polymerization of the triple rods (closed symbols) and triangle particles (open symbols). Squares mark the diameter of spheroid b relative to spheroid a (d _t /d _a ), and circles mark the diameter of spheroid c relative to spheroid a (d _c /d _a ). Time=0 seconds corresponds to the appearance of the new phase. Without wishing to be bound by theory, it is believed that the difference in phase separation time is likely related to the viscosity difference in swollen dimers. The swollen dimer that forms the triangle likely has a higher viscosity due to its higher cross-linking density. Thus the flow of monomers to form the third spheroid may be slowed by the existing cross-linked network.

[0071 J Using the insights gained from studying the formation of triple rod and triangle particles, additional particle shapes, including cones and diamonds, as shown in Figs. 3C and 3D. The cones were produced similarly to triple rods, but with a higher volume of monomers in the final swelling stage ( [DVB\ /[DVB] ₀ =0.7 ([DVB] ₃ = 1 vol%, [DVB] _b = 0.7 vol%) The diamonds were synthesized similarly to the triangle particles, but with higher values of [Z)FS] ₀ and [Z)FS] ₄ (1.2 and 1.32 vol%, respectively, [Z)FS] _n /[Z)Fs] ₀ =1.1). The stronger elastic contraction gave rise to two new spheroids rather than one new spheroid. The two new spheroids appeared opposite each other on the perpendicular axis of the dimer. This illustrates that the fabrication method allows the preparation of colloid clusters, such as rods and diamonds, that would not be possible in a drop clusterization process.

[0072] This approach for synthesizing non-spherical particles is not only very reproducible but also produces high yields in comparison with other current methods.

After polymerization, typical batches contain ~10 ¹⁰ particles mL ^'1 . These volumes can be easily scaled up; moreover, because no sorting is required, the yield of this technique is considerably higher than other methods.

[0073] In summary, cross-linking density gradients can be used to overcome the effect of surface tension and provide reproducible directionality to phase separations. Surface tension scales with particle surface area, while the particle cross-linking, or elasticity, scales with particle volume; therefore, the balance of these two effects will be size dependent. In one or more embodiments, particles can be fairly large (e.g., about 5 μm), however, in other embodiments smaller particles are contemplated. To make particles at smaller length scales, a lower particle surface tension can be employed so that it does not dominate the effect of elasticity. The results presented herein illustrate the potential usefulness of synthesizing non-spherical particles at larger length-scales; surface tension effects will need to be addressed in order to synthesize non-spherical particles with nanometer size scales.

Fabricating Chemically Anisotropic Non-spherical Particles

[0074] Methods of making "dimer" particles can also be modified to allow the fabrication of chemically anisotropic, e.g., amph philic, non-spherical particles. Here, the surfaces of one or more spheroids in the particles have different solubility characteristics from each other. These different solubilities may arise from the spheroids having different compositions, and/or may arise from modifications made to the surfaces of one or more of the spheroids. In contrast, the spheroids of conventional dimer particles typically have comparable solubilities, because they both are made of hydrophobic polymer without further modifications.

[0075] Fig. 8 illustrates a method (800) of fabricating complex particles (trimers or larger) of controlled shape. First, approximately spherical seed particles with a first polymer composition and having a first crosslinking density v _a are provided or fabricated (801), for example as described in the incorporated literature references, or as described above. In one or more embodiments, next the seed particles are treated to

provide a reactive surface having a selected functional group. The functional group may be selected to provide the particle with a desired reactivity or surface property. By way of example, the seed particles are next copolymerized with or otherwise attached to molecules that have active sites (802). The molecules have one end that favors attachment to the seed particles, e.g., covalent bonding through copolymerization to the first polymer composition, and one end that includes an active site. The active sites substantially remain on the surface of the seed particles. Next, the active sites are reacted with molecules having a desired hydrophilicity (803). The hydrophilicity of the molecules is selected to provide a desired overall amphiphilicity in the finished particles, as discussed in greater detail below. Other conventional means of modifying the surface chemistry of a particle may be used. Next, the seed particle is swollen with a monomer, as described in greater detail above or as in the incorporated literature references (804). Next, the monomer is polymerized to form a second polymer composition having a second crosslinking density v _/ , (805), and thus form a second spheroid. The second crosslinking density v _/ , may be defined, for example, by providing a particular percentage of crosslinking agent with the monomer. Note that the second crosslinking density need not be highly controlled if a third spheroid will not be grown from the resulting dimer. However, if a higher order non-spherical particle is desired, then the first and second crosslinking densities may be selected to provide a desired cross-linking gradient and thus define the growth direction of additional spheroids that may be added as described in greater detail above. Note that the steps can take place in a different order. For example, the active sites can be reacted (803) after polymerization (805). In other embodiments, the particles can be further chemically modified by reacting the surface of the second polymer composition with a suitable reagent to modify the surface of the newly formed spheroid. The reactive molecules may be selected to be selectively reactive with the second polymer composition. Alternatively, the reactivity of the first polymer composition may be sufficiently protected due the prior surface modification, that the second polymer composition is selectively modified in the second surface modification step.

[0076] When the second polymer composition phase separates from the first polymer composition, thus forming the second spheroid, the molecules that were initially attached to the seed particle will substantially remain with the seed particle in the first spheroid. Specifically, before the phase separation, the first polymer is copolymerized with or otherwise covalently bonded to reactive monomers that can contain a wide variety of functional groups, including, hydroxyl, amine, thio, imine, silane, carboxyl, sulfate, sulfonate, and so on. These functional groups are covalently linked to the network of the first polymer so that they can stay in the network during the phase separation. This approach gives rise to the dimers that have two different surface properties and have selective reactivity to other functional molecules.

[0077] Using this rationale, the steps of swelling and polymerizing with a selected crosslinking density can be repeated to fabricate collections of particles having a desired number of location-controlled spheroids, each having a desired hydrophilicity or other chemical functionality.

[0078] Fig. 1 1 schematically illustrates steps in a variation of the method of Fig. 8. First, a seed particle with copolymerized molecules having active sites is provided (1 101). In one example, the seed is CPS copolymerized with one or more silane groups, for example, by swelling the seed particle with styrene monomer and a silane group- including monomer (e.g., 3-(trimethoxysilyl) propyl acrylate or vinyl silane), and then polymerizing the swollen particle to give rise to a silane group-covered CPS particle. The seed particle 1 102 is then swollen with monomer. Next, first and second spheroids are created during the polymerization step (1103). The size of the second spheroid relative to the first spheroid, and the extent to which the first and second polymer compositions foπn an IPN, can be controlled by adjusting process parameters, as described above and in the incorporated literature references. Next, the active site of the first spheroid is coupled to a molecule having a desired hydrophilicity (1 104). For example, the silane groups in the example above can be coupled to amine groups, which are hydrophilic, by using an amine group-containing silane coupling agent. This yields an amphiphilic dimer.

[0079] Fig. 12A is a scanning electron microscope (SEM) image of a collection of spherical particles treated with amine-groups. Fig. 12B is an SEM image of a collection of amphiphilic PS dimer particles, fabricated using the method of Fig. 1 1, that have spheroids selected to be of different sizes (see inset) that give rise to a packing parameter (P _pa ckmg) of about 0.6. P _pac king is defined to be v/aol _c , where v is the hydrocarbon volume, a<) is the optimal area, and l _c is the critical chain length. The packing parameter reflects the spontaneous curvature that would be achieved if these amphiphilic particles are used as surfactants to stabilize emulsions. By adjusting the packing parameter, the spontaneous curvature of the emulsion droplets can be varied, and hence the size and shape of the droplets can be more precisely controlled. In some embodiments, selection of the packing parameter thus imparts the particles with a selected surfactant-like behavior. For example, particles with a packing parameter of between 0.33 and 1 can be used to stabilize an oil-in-water emulsion. If the packing parameter is near 0.33, the resulting emulsion has a larger curvature, thus forming a smaller emulsion; by contrast, when the packing parameter is near 1, the emulsion has a smaller curvature, thus giving rise to a bigger emulsion. The packing parameter of the particles can be selected by selecting, among other things, the relative sizes of the spheroids in the particles, e.g., by adjusting the amount of monomer and/or cross-linker used to fabricate the spheroids.

[0080] Fig. 12C is an SEM image of a collection of amphiphilic PS dimer particles, fabricated using the method of Fig. 1 1, that have spheroids selected to be of different sizes that give rise to a Ppack _mg of about 0.8. Fig. 12D includes both a bright-field microscope image (left) and a fluorescence microscope image (right) at the same location, for dimer particles in which the amine groups introduced on one of the spheroids are selectively labeled with fluorescein isothiocyanate. The fluorescence microscopic image in Fig. 12D shows that only one spheroid of the dimer particles is covered by hydrophilic amine groups, thus confirming that the dimer particles are amphiphilic.

[0081] Figs. 13A-13C are OM images of amphiphilic PS dimer particles, fabricated using the method of Fig. 1 1, that have a P _paCk i _ng of about 0.6 (e.g., as illustrated in Fig. 12B). The particles are adsorbed at the interface of droplets of hexadecane in water of different shapes. Fig. 13A illustrates particles adsorbed at the interface of a spherical hexadecane droplet. Fig. 13B illustrates particles adsorbed at the interface of an ellipsoidal hexadecane droplet. Fig. 13C illustrates particles adsorbed at the interface of a cylindrical hexadecane droplet.

[0082] Figs. 13A-13D illustrate that the wettability of the oil with the hydrophobic spheroid of the dimer particles can change the shape of the resulting emulsion drops. The shape of the resultant emulsion drops is controlled by the wettability of the hydrophobic spheroid with the oil. When the wettability is either too high or too low, the dimer particles lie flat on the interface. When hydrophobic particle has a wettability selected appropriate to the oil, and the hydrophilic spheroid has a wettability selected appropriate to the water phase, the dimer particles can stand up on the interface to stabilize the emulsion drops. With this condition, the hydrophobic spheroids can come closer to each other making a more compact structure on the oil phase, possibly due to van der Waals interactions; this provides an improved stability of the emulsion droplets. This can also lead to deformation of the interface to form nonspherical emulsion drops.

[0083] The fact that the shape of the droplet can be controlled confiπns the surfactant-like properties of these amphiphilic particles. This promises a unique form of emulsion stabilization, using particles rather than surfactants. Such emulsions are likely to be far more stable and robust than surfactant-stabilized emulsions, and much more versatile. Moreover, by controlling the shape of the amphiphilic particles, the characteristic size and shape of the droplets can be controlled, adding considerable flexibility to the system.

Uses of Non-Spherical Particles

[0084] The ability to produce large quantities of uniform non-spherical particles enables the exploration of many new applications. For example, the fabrication method

allows the packing densities of particles of different shapes to be compared. Fig. 10 is a photograph of the results of simple packing experiments with three particle types: spherical, triple rod, and triangle. The individual particle volumes (approximately 38 μm ³ ), overall volume fractions, and dispersion volumes were maintained constant for all particle types. Each dispersion was prepared in 0.05 w/v % Fluronic F-68 aqueous solution at 23.8 vol%. The particle dispersions were completely sealed in round capillaries (inner diameter ~2.1 mm). The particles sedimented until there were no changes in the packed volume (about 35 days). To enhance packing, the particle-packed capillaries were gently sonicated several times during sedimentation. As the particles sedimented, differences in packing densities of the different particle types became readily apparent to the eye. The volume fraction of spherical particles reached a packing density of approximately φ « 0.64, close to the expected random close-packing value. Remarkably, however, the rods and triangles packed more densely, up to approximately φ « 0.67. This result is consistent with previous studies showing that nearly spherical ellipsoids pack more efficiently than spheres (see the incorporated literature references).

[0085] Non-spherical particles can also be used in rheological applications. The non-spherical particles have been found to affect the viscosity of solutions differently, depending on their concentrations, because it changes packing properties and interactions between them under shear. For example, non-spherical particles show a lower viscosity than spherical particles in the dense suspensions of a same concentration. Thus, particle shape at least partially determines the rheological property of particle suspensions, especially at a high concentrations.

[0086] In another application, the non-spherical particles can be used to monitor fluid dynamics. Because they are small, but can be seen with optical microscopy, their motion in all three dimensions, including their rotations in all three dimensions, can be observed to change with the flow of a fluid. The particles can further be modified by including a magnetic material or conductive polymer in the spheroids or on their

surfaces, and their three-dimensional motion (including rotation) can be monitored. In contrast, while the position of a comparable spherical particle can readily be monitored, because the particles are isotropic it is generally not possible to monitor their rotation. The presence of back-flow, for example, may be difficult to observe with a spherical particle, but would be readily observable with a non-spherical particle.

[0087] Non-spherical particles can also be used as "building blocks" for superstructures, such as colloidosomes. Conventionally, colloidosomes are formed by assembling spherical particles, that have uniform surfaces (e.g., having a particular hydrophilicity) at an interface. The interface is typically curved, which creates defects that prevent the particles from packing ideally, thus potentially weakening the structure. However, the shape of non-spherical particles can be selected to pack in preferable arrangements at an interface, so as to alleviate defects and form a more stable structure. For example, "cone" structures such as those illustrated in Fig. 3c may pack particularly tightly at an interface of a particular curvature.

[0088] Additionally, the hydrophilicity and/or hydrophobicity of the different parts of the particles can be controllably modified, creating a surfactant-like structure. Amphiphilic non-spherical particles are potentially useful as colloid surfactants, e.g., in oil-in-water, gas-in-liquid, liquid-in-gas, and other types of immiscible systems. Because the properties of the particles can be selectively tuned, the particles can be fabricated to remain at an interface with very high stability. For example, they may be able to impart improved stability to foams and emulsions owing to their strong adsorption at interfaces and may significantly alter the mechanical properties of these systems. Furthermore, it may be possible to tune the curvature of such emulsions by modifying the geometry of unit amphiphilic particles.

[0089] A Pickering emulsion includes two immiscible phases, which have an interface tension between them. The surface tension of a spherical particle with a uniform surface at that interface is typically less than the surface tension of the interface itself, and so tends to not stably remain at the surface. In contrast, an anisotropic non-

spherical particle will remain at the interface because its two parts can be selected to remain stably in the two phases. Conventional Pickering emulsions can be formed with particles having diameters of approximately 10 μm size, whereas Pickering emulsions can be readily formed with non-spherical particles having diameters of less than 1 μm, as illustrated in Example 2. This is because the absorption energy (the amount of energy to pull the particle away from the interface) for non-spherical amphiphilic particles is much higher than that for a sphere with a uniform surface, with a comparable surface area. The colloidosomes thus formed are sufficiently stable that they may be readily dried to form a powder, and then redispersed in appropriate solvents, without damaging their structures. Appropriate solvents include those that will wet the surface of the as-formed colloidosome. Thus, if the colloidosome is formed at the interface between a droplet of hydrophilic liquid and a bath of hydrophobic liquid, the outer surface of the colloidosome will be hydrophobic, and the colloidosome can therefore be re-dispersed in an appropriate hydrophobic solvent. Conversely, if the colloidosome is formed at the interface between a droplet of hydrophobic liquid and a bath of hydrophilic liquid, the outer surface of the colloid will be hydrophilic, and the colloidosome can therefore be re-dispersed in an appropriate hydrophilic solvent, such as water. Colloidosomes can also be fabricated at air/water or air/organic solvent interfaces, because air phase is hydrophobic. For example, if air bubbles are generated in the presence of amphiphilic particles in water, the hydrophobic part of the particles go into the air phase and assemble at the interface, thus stabilizing the bubbles. Or, by selecting appropriate surface chemistries and sizes for the spheroids of the non-spherical particles, those particles can be made to self-assemble in a single-phase solvent such as water, forming a colloidosome that is water-soluble and is filled with an aqueous solution. Optionally, the non-spherical particles can be bonded to each other after assembling them, for example as described in PCT Publication No. 02/47665, filed December 7, 2001 and entitled "Methods and Compositions for Encapsulating Active Agents," the entire contents of which are incoiporated herein by reference. The stability of superstructures such as colloidosomes can be assessed by quantifying whether

smaller colloidosomes coalesce over time into larger colloidosomes. It has been observed that colloidosomes formed of non-spherical particles do not tend to coalesce.

[0090] Additionally, while many conventional surfactants such as soap may be irritating to the skin, here the non-spherical amphiphilic particles are generally mild, safe to use, and non-irritating to the skin. The non-spherical amphiphilic particles can be incoiporated into cosmetic formulations in the place of conventional surfactants. In cosmetic formulations, conventional surfactants may be added to stabilize emulsions in any storage conditions for a long time. But, conventional surfactants that we can use are limited due to safety issues. For example, ionic surfactants can typically only be used restrictively, because their molecular weights are so small that they partially penetrate the skin and induce irritation. Also strong ionic groups on them disturb the skin structure, resulting in some serious side effects, including ticklishness, stabbing, and inflammation. The non-spherical amphiphilic particles are generally nonionic surfactants that can assemble at the interfaces and effectively stabilize emulsions, and they are very big in comparison with conventional surfactants, providing excellent safety to skin.

[0091] One application of superstructures such as colloidosomes is the delivery of compounds, such as drugs. In one embodiment, one spheroid of the non-spherical particles is treated with an environment-sensitive material, such as a gel. The material swells in response to an environmental stimulus, such as temperature, pH, or some other condition. Then, when the colloidosome is exposed to the stimulus, the material will swell, changing the packing of the non-spherical particles in the colloidosome and creating pores through which the compound can flow. By controlling the pore size, by tuning the stimulus, the flow of the compound can be controlled. Depending on the relative hydrophilicities/hydrophobicities of the spheroids of the non-spherical particles, the colloidosome can be fabricated to be water-soluble, with a hydrophobic phase inside carrying, for example, a hydrophobic drag that would otherwise be relatively difficult to deliver.

Example 1

[0092] The following example is an illustrative embodiment of a method of making trimer particles, as discussed above in the section entitled "Controlled Synthesis of Higher Order Non-Spherical Particles "

[0093] Particles were produced with a repeated seeded polymerization method. In all swelling processes, 20 vol% seed particles were dispersed in a 1% w/v PVA (87- 89 % hydrolyzed, 8.5χl0 ⁴ ~1.24xl0 ⁵ g-mol ^"1 , Aldrich) aqueous solution. A 20 vol% monomer emulsion was also prepared in a 1 % w/v PVA aqueous solution by homogenizing at 8x10 ³ rpm and mixed with the seed particles dispersion. The monomer solution consisted of styrene, divinylbenzene (DVB, 55% isomer, Aldrich), and initiator (0.5 wt%, V-65B, 2,2'-azodi (2,4'-dimethylvaleronitrile), Wako). The mixture was tumbled at speed of 40 ipm for more than 10 h at room temperature to allow the seed particles to swell. Then, polymerization was performed by tumbling again at 100 rpm for 8 h at 70 ⁰ C in an oil-filled bath. After the final polymerization, substantially all unreacted monomers and additives were removed by repeated washing with methanol.

[0094] In each step of the swelling, the concentration of DVB was varied with respect to the total monomer volume. In the synthesis of spherical cross-linked PS seed particles, a 2.5 mL dispersion of monodisperse PS templating particles (~1.5 μm) was swollen by the monomer mixture (2 mL, [DFJj] ₀ = 1 vol%). In the synthesis of diraers, a 2.5 mL dispersion of cross-linked PS seed particles was swollen again with the monomer mixture (1.5 mL, to 1.1 vol%). Finally, the dimers (2.5 mL) were swollen again with the monomer mixture (1.5 mL, [D FZ?^ =0.5 to 1.2 vol%, plus 0.5 mL toluene). Although was varied in the experiments reported herein, additional experiments confirmed that the trimer particle morphology is essentially independent of [DFi?]. , just as dimer morphology is independent of [DFS] ₄ . Toluene

was added to the monomer mixture in step c to make the phase separation more favorable.

[0095] The non-spherical particles were observed with a field emission scanning electron microscope (FE-SEM, Leo 982) at an acceleration voltage of IkV. SEM samples were prepared by drying 0.1 wt% of purified particles on thin glass and directly examined without further coating of a conductive layer.

[0096] In the optical microscopy experiments, the monomer-swollen dimers were sealed in the flat glass capillaries (100 μm inner diameter) and mounted on a temperature-controlled stage of an optical microscope (Leica) equipped with a digital camera (Hamamatsu, C4742-95) that was operated by Simple PCI software (Compix). Phase separation was monitored at 70±0.1 ⁰ C.

Example 2

[0097] The following example is an illustrative embodiment of a method of making amphiphilic dimer particles, as discussed above in the section entitled "Fabricating Chemically Anisotropic Non-Spherical Particles. ^' ' ^' '

[0098] First, to incorporate specific reactive sites, 5 vol% glycidyl methacrylate (GMA) was copolymerized to CPS seed particles. The epoxy rings of GMA units on the CPS particles offer reactive sites for hydrophilic chemicals that have active hydrogen (here, poly(ethylene imine), PEI was used). Moreover, they also lower the surface tension of the swollen particles by partial hydrolysis by water molecules at high temperatures. Fig. 9A is an optical microscope image of asymmetrically phase- separated PS particles (CPS/Styrene = 1/3, w/v). As Fig. 9A shows the lowered surface tension allows the swollen CPS particles to expand and diminishes the stress due to the Laplace pressure, which is responsible for the formation of snowman-shaped particles. Fig. 9B is an optical microscope image of symmetrically phase-separated PS dimer particles (CPS/Styrene = 1/4, w/v), with 5 vol% glycidyl methacrylate (GMA) copolymerized into the CPS particles. As Fig. 9B illustrates to compensate for this

effect, the monomer swelling ratio, α, was increased from 3 to 4, resulting in an increase in the elastic stress by -2.5 times, thereby enhancing phase separation. The epoxy rings stay in the CPS network during the phase separation, and do not exist on the newly-polymerized spheroid.

[0099] Finally, selective reaction of PEI with the epoxy rings imparts amphiphilicity to the dimer particles. Fig. 9C is an SEM image of amphophilic PS dimer particles obtained by reacting the epoxy groups of GMA, copolymerized into the CPS seed particles, with poly (ethylene imine) (PEI, 2.5χ lO ⁴ gmol ^"1 ). Fig. 9D is a fluorescence image achieved by labeling fluorescein to PEI, demonstrating that the dimer particles indeed consist of two different spheroids; hydrophilic PEI-coated PS and hydrophobic PS. The inset to Fig. 9D is a schematic of the as-fabricated amphiphilic particles, with hydrophilic PEI groups attached to one spheroid of the dimer. This amphiphilicity makes the particles strongly adsorb at interfaces, as illustrated by the solid shell of adsorbed particles on the surface of a water drop in 1 -octanol shown in Figure 9E.

Incorporated Literature References

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[0101] A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.

[0102] What is claimed is: