WO2019088922A1 - Hollow silica spheres with raspberry-like structure and method for preparation thereof - Google Patents

Abstract

According to the present disclosure, a method of synthesizing hollow inorganic microparticles each having a raspberry-like structure is provided. The method comprises mixing a solution comprising microparticles and submicroparticles to obtain composite particles, wherein each of the composite particles comprises one microparticle having the submicroparticles disposed thereon, forming an inorganic layer on each of the composite particles, and removing the composite particles to obtain the hollow inorganic microparticles each having raspberry-like structure. A hollow inorganic microparticle having a raspberry-like structure, wherein the hollow inorganic microparticle comprises a hollow microparticle having hollow submicroparticles disposed thereon, is also disclosed.

Description

HOLLOW SILICA. SPHERES WITH RASPBERRY-LIKE STRUCTURE AND METHOD FOR PREPARATION THEREOF

Cross-Reference To Related Application

[0001] This application claims the benefit of priority of Singapore Patent. Application. No. 10201708879P, filed 30 October 2017, the content of it being hereby incorporated by reference in its entirety for all purposes.

Technical Field

[0002] The present disclosure relates to a method of synthesizing micrometer-sized hollow inorganic particles with raspberry-like structure. The present disclosure also relates to such hollow inorganic microparticles.

Background

[0003] Silica hollow spheres (SHS) have attracted tremendous interest as a special class of material due to their mechanical stability, thermal stability, pH insensitivity, ease of modification, low toxicity, and low density. These particles can be applied in wide areas such as energy generation and storage, catalysis, heavy metal ions separation, drug delivery and controlled release, etc. Commercially available particles have their limitations. For instance, commercial polymer microbeads may be uniform in size but they tend to be neither useable for high temperature applications nor with organic solvents. Commercial silica particles are made of inert material but they have high density and are not suitable for suspensio based reactions. Commercial hollow glass beads are made of inert material and. have low density but they tend to lack size uniformity. SHS, as a special group of particles, are made of inert material, have low density and can be uniform in size. However, SHS tend to be in the subraicroraeter size range (siibmicroSHS). Micrometer-sized SHS (MicroSHS), in contrast thereto, may be synthesized to have uniform size in micrometer size range, low density, of inert material suitable for use at high temperature or in organic solvents.

[0004] Conventionally, SHS may be prepared by methods using soft or hard templates.

[0005] Soft templates may be micelles or vesicles for forming the SHS via a sol-gel method. However, soft, templates may lead to difficulty in terms of controlling the resultant particles' size, morphology and dispersity, owing to the complexity of the sol- gel process. The procedures may require very stringent synthetic conditions in terms of, for example, synthesis sequence and time precision. The synthesis procedures may also require surfactants that are typically expensive or commercially unavailable. In addition, the resultant spheres tend to be multi-dispersed.

[0006] Meanwhile, polymer particles are typically used as hard templates since SHS prepared by methods using hard templates tend to provide better control over the resultant particle's size and lead to narrower size distribution. Methods involving hard templates may be optimized through reaction parameters, for example, reaction pH, amount of silica precursor, and/or reaction time. Currently, SHS synthesized using hard templates tend to be in the sub-micrometer range. This may be due to the difficulty in controlling the homogeneous nucleation during the coating process. Producing micron- sized SHS (microSHS) remains a challenge when large micron-sized particles are used as templates.

[0007] There is thus a need to provide a solution for synthesizing microSHS that ameliorates and/or resolves one or more of the issues and/or limitations mentioned above.

Summary

[0008] In one aspect, there is provided for a method of synthesizing hollow inorganic microparticles each having a raspberry-like structure, the method comprising:

mixing a solution comprising microparticles and submicroparticles to obtain composite particles, wherein each of the composite particles comprises one microparticle having the submicroparticles disposed thereon;

forming an inorganic layer on each, of the composite particles; and

removing the composite particles to obtain the hollow inorganic microparticles each having a raspberry-like structure.

[0009] In another aspect, there is provided for a hollow inorganic microparticle having a raspberry-like structure, wherein the hollow inorganic microparticle comprises a hollow microparticle having submicroparticles disposed thereon. Brief Description of the Drawings

[§010] The drawings are not necessarily to scale, emphasis instead generally being placed upon illustrating the principles of the invention, hi the following description, various embodiments of the present disclosure are described with reference to the following drawings, in which:

[0011] FIG. 1A is a schematic illustration of conventional, hard-templating method for synthesis of submicron-sized silica hollow spheres (submicroSHS) and the attempt to use the conventional hard-tempating method for the synthesis of micron-sized silica hollow spheres (microSHS).

[0012] FIG. IB is a schematic illustration of the present hard-templating method for synthesis of microSHS having submicroSHS on the surfaces presenting raspberry-like structure.

[0013] FIG. 2 shows a transmission electron microscopy (TEM) image of submicroSHS synthesized, using conventional hard-templating method. PS-COOH particles having an average diameter of 220 nra were used as the hard templates.

[0014] FIG. 3 A shows a TEM^' image of silica shells produced using conventional hard- templating method. The silica shells were produced using PS-COOH microspheres having an average diameter of 6 μηι. as the hard templates. The scale bar denotes 1 μηι.

[0015] FIG. 3B shows a higher magnification, of the TEM image of FIG. 3 A. The scale bar denotes 100 nm.

[0016] FIG. 3C shows a TEM image of silica shells produced using conventional hard- templating method. The silica shells were produced using PS-NH₂ microspheres having an average diameter of 6 μηι as the hard templates. The scale bar denotes 1 μηι.

[0017] FIG. 3D shows a higher magnification of the TEM image of FIG. 3C. The scale bar denotes 100 nm.

[0018] FIG. 3E shows a TEM i mage of silica shells produced using conventional hard- templating method. The silica shells were produced using PS microspheres having an average diameter of 6 pm as the hard templates. The scale bar denotes 1 μιη.

[0019] FIG. 3F shows a higher magnification of the TEM image of FIG. 3E. The scale bar denotes 1.00 nm.

[0020] FIG. 4A is a scanning electron microscopy (SEM) image of PS-COOH microspheres before mixing with PS-COOH submicron-sized particles. The microspheres have an. average diameter of 6 μχη and the submicron-sized particles have an average diameter of 220 nm. The scale bar denotes 1 pm.

[1)021] FIG. 4B is a SEM image of PS-COOH microspheres after mixing with PS- COOH submicron-sized particles. The surface morphology can be observed. The microspheres have an average diameter of 6 pm and the submicron-sized particles have an average diameter of 220 nm. The scale bar denotes 1 pm.

[0022] FIG. 4C is a SE : image of PS-NH2 microspheres before mixing with PS- COOH submicron-sized. particles. The microspheres have an average diameter of 6 pm and the submicron-sized particles have an. average diameter of 220 nm. The scale bar denotes 1 μηι

[0023] FIG. 4D is a SEM image of PS-NH2 microspheres after mixing with PS-COOH submicron-sized particles. The surface morphology can be observed. The microspheres have an average diameter of 6 pm. and the submicron-sized particles have an average diameter of 220 nm. The scale bar denotes 1 pm.

[0024] FIG. 4E is a SEM image of PS microspheres before mixing with PS-COOH submicron-sized particles. The microspheres have an average diameter of 6 pm. and the submicron-sized particles have an average diameter of 220 nm. The scale bar denotes 1 p m.

[0025] FIG. 4F is a SEM image of PS microspheres after mixing with PS-COOH submicron-sized particles. The surface morphology can be observed. The microspheres have an average diameter of 6 pm and the submicron-sized particles have an average diameter of 220 nm. The scale bar denotes 1 pm.

[0026] FIG. 5A shows a TEM image of microSHS synthesized using the present hard- templating method, demonstrating that microspheres with negative surface charges could be used in this method. PS-COOH microspheres (average diameter of 6 pm.) were mixed with PS-COOH particles of 220 nm and used as the hard templates for silica coating. The scale bar denotes 1 pm.

[0027] FIG. 5B shows a higher resolution TEM image of FIG. 5A. The scale bar denotes 100 nm.

[0028] FIG. 5C shows a TEM image of microSHS synthesized using the present hard- templating method, demonstrating that microspheres with positive surface charges could be used in this method. PS -NH₂ microspheres (average diameter of 6 pm) were mixed with PS-COOH particles of 220 run and used as the hard templates for silica coating. The scale bar denotes 1 μη .

[0029] FIG. 5D shows a higher resolution TEM image of FIG. 5C. The scale bar denotes 100 nm.

[0030] FIG. 5E shows a TEM image of microSHS synthesized using the present hard- templating method, demonstrating that microspheres with neutral surface charges could be used in this method. PS microspheres (average diameter of 6 μιη) were mixed with PS-COOH particles of 220 nm and used as the hard templates for silica coating. The scale bar denotes 1 μηι.

[0031] FJG. 5F shows a higher resolution TE image of FIG. 5E. The scale bar denotes 100 nm.

[0032] FIG. 6A shows a TEM image of microSHS synthesized using the present hard- templating method, demonstrating that sizes of both the micron- and submicron-hollow spaces could be tuned by changing the sizes of d e micron- and submicron-templating particles. PS-COOH microspheres (average diameter of 6 μιτι) were mixed with PS- COOH particles (average diameter of 85 nm) and used as the hard templates. The scale bar denotes 1 μιη.

[0033] FIG. 6B is a higher resolution TEM image of FIG. 6A. The scale bar denotes 100 nm.

[0034] FIG. 6C shows a TEM image of microSHS synthesized using the present hard- templating method, demonstrating that sizes of both the micron- and submicron-hollow spaces could be tuned by changing the sizes of the micron- and submicron-templating particles. PS-COOH microspheres (average diameter of 10 μπι) were mixed with PS- COOH particles (average diameter of 220 nm) and used as the hard templates. The scale bar denotes 1 μη .

[0035] FIG. 6D is a higher resolution TEM image of FIG. 6C. The scale bar denotes 100 nm.

[0036] FIG. 6E illustrates the density of submicron particles on the micron particles based on. FIG. 6A.

[0037] FIG. 6F illustrates the density of submicron particles on the micron particles based on FIG. 6C, [0038] FIG. 7A shows a SEM image of microSHS templated using mixture of 6 μηι PS-COOH microspheres (average diameter of 6 μιη) and PS-COOH particles (average diameter of 220 nm). The scale bar denotes 10 μιη.

[0039] FIG. 7B shows a higher resolution image of FIG. 7A. The scale bar denotes 1

Detailed Description

[0040] The following detailed description refers to the accompanying drawings that show, by way of illustration, specific details and embodiments in which the invention. may be practiced.

[0041] Features that are described in the context of an embodiment may correspondingly be applicable to the same or similar features in the other embodiments. Features that are described in the context of an embodiment may correspondingly be applicable to the other embodiments, even if not explicitly described in these other embodiments. Furthermore, additions and/or combinations and/or alternatives as described for a feature in the context of an embodiment may correspondingly be applicable to the same or similar feature in the other embodiments.

[0042] The present disclosure relates to a method of synthesizing micrometer-sized hollow inorganic particles each having a raspberry-like structure. The present method circumvent the limitations as described above. A particle having a raspberry-like structure refers to a particle that has an uneven porous surface or shell, where the uneven surface is due to the random disposition of other smaller sized particles, rendering the surface of the particle uneven. Such a raspberry-like structure is depicted in, for example, FIG. IB, FIG. 6C, FIG. 7B, etc.

[0043] The present method is straightforward when compared to conventional methods, as the present method involves, as an initial step, only the mixing of two types of particles before an inorganic layer (e.g. silica) coating to form the hollow inorganic microparticles each having a raspberry-like structure. The first type of particles differ from the second type of particles in that they are of a different average diameter. For instance, the first type of particles may be micron-sized while the second type of particles may be submicron-sized. Micron-sized particles, as used herein, refer to particles having an average diameter ranging from 1 μτη to 100 μιη. Submicron-sized particles, as used herein, refer to particles having an average diameter that is less than 1 μηι but at least 1 run.

[0044] In the present disclosure, the expressions "micron-sized particles" and "micron particles" are used interchangeably with "microparticles", and the expressions "submicron-sized particles" and "submicron particles" are used interchangeably with "submicroparticles". The particles, including the microparticles, submicroparticles, resultant hollow inorganic microparticles, may be substantially spherical. This means that, in some instances, the particles may be perfectly spherical. In some instances, the particles need not be a perfect sphere. The expressions "particle" and "sphere" may be used interchangeably in the present disclosure.

[0045] In the present disclosure, although the term, "diameter" is used normally to refer to the maximal length of a line segment passing through the center and connecting two points on the periphery of a sphere, it is also used herein to refer to the maximal length of a line segment passing through the center and connecting two points on the periphery of particles which are not perfectly spherical. The average diameter may be calculated by dividing the sum of the diameter of each particle by the total number of particles.

[0046] The mixing of two types of particles having two different average diameters that is mentioned above, allows for interaction between, the microparticles and submicroparticles, and the surface of the microparticles may be decorated with the submicroparticles, thereby forming micron-sized hierarchical templates used for forming hollow inorganic microparticles each having the raspberry-like structure. Each of the template particles may have a raspberry-like structure and morphology due to the arrangement of submicroparticles on each microparticle. The coverage of submicroparticles on the outer surface of each microparticle may be variable. For example, the submicroparticles may substantially cover the outer surface of the microparticle, which in some instances, the submicroparticles may completely cover the outer surface of the microparticle. In other instances, the submicroparticles need not cover the entire outer surface of the microparticle. The word "substantially" does not exclude "completely" e.g. a composition which is "substantially free" from Y may be completely free from Y. Where necessary, the word "substantially" may be omitted from the definition of the invention. [0047] To form, hollow inorganic microparticles from, the hierachical templates, the hierarchical templates may be coated with an inorganic layer. The hierachical templates are subsequently removed, leaving behind the inorganic layer forming the micron-sized hollow spheres (microHS) covered with submicron-sized HS (siibmicroHS). To further elaborate, the resultant particle is a hollow particle in the micxonmeter size range (i.e. 1 μ^ηι to 100 μπι) covered with smaller hollow particles that are in the submlcrometer size range (i.e. at least 1 nm but less than 1 μπι), as shown in FIG. IB. Both the hollow particle in the micrometer size range and hollow particles in the submicrometer size range may have an inorganic layer formed as the inorganic shell, for example, a silica shell. This inorganic shell is illustrated by the thick black circles in. FIG. IB, the structure of submicroparticles on a microparticle gives rise to the raspberry-like structure. Microparticles decorated/covered with submicroparticles on their surfaces form, the composite particles, for inorganic layer coating. The inorganic layer or shell forms on the surfaces of the submicroparticles as well as surfaces of the microparticles that are exposed (i.e. not covered by the submicroparticles). As a non-limiting example, the resultant particle may be a micron-sized silica hollow sphere (microSHS) covered with submicron-sized silica hollow spheres (submicronSHS), presenting the raspberrylike surface morphology. Formatio of the resultant hollow silica core-shell particles may be attributed to an increase in the surface-area-to-volume ratio of the templates when the microparticles are decorated with the smaller submicroparticles, which in turn enhances coating of the inorganic layer onto the templates. This is in contrast to conventional methods that use only microparticles composed of one average diameter, as such microparticles have lower surface-area-to-volume ratio. Each of the resultant hollow inorganic microparticles may have a raspberry-like structure and morphology imparted by the template.

[0048] The present method is advantageously versatile as it can. be applied to microparticles with negative, neutral or positive surface charges, requiring only a simple mixing with submicroparticles. In other words, no surface modification, no additional and/or special treatment of the particles, is required to form the hierarchical composite templates. For example, the surface of the microparticles need not. be adapted to be able to form covalent bondings with the materials to be coated thereon. [§§49] The present method is also advantageous as it offers good size controllability (i.e. tunahility) at both the micron-scale and submicron-scale by simply changing the sizes of the microparticles and subniicroparticles used to form the template. The resultant particles formed have a narrow diameter distribution.

[0050] The present method is further advantageous as the resultant particles have a low density and. high surface-area-to-volume ratio. The earlier is due to the hollow particles formed when the templates are removed and the latter is due to the raspberry-like structure imparted from the template. The high surface-area-to-volume ratio provides a high loading capacity for any materials to be grafted onto the resultant particles.

[0051] The present method can. be extended to form hollow silver, palladium, or gold particles apart from silica ones, as the templates can be used for coating with other materials besides silica, such as silver, palladium, or gold.

[0052] Details of the various embodiments are now described below.

[0053] Various embodiments of the present disclosure relates to a method, of synthesizing hollow inorganic microparticles each having a raspberry-like structure. The method may comprise mixing a solution, comprising microparticles and subniicroparticles to obtain composite particles, wherein each of the composite particles comprises one microparticle having the subniicroparticles disposed thereon, forming an inorganic layer on each of the composite particles, and removing the composite particles to obtain the hollow inorganic microparticles each having a raspberry-like structure. The microparticles and/or the subniicroparticles do not require surface modification according to various embodiments. This means thai the use of surfactants is circumvented with the present method.

[0054] In the present method, a mixture comprising two types of particles may be first fo.rm.ed. These two types of particles differ in terms of their average diameter. As mentioned above, the first type is the microparticle and the second type is the submicroparticle. The micropaiticles may comprise an average diameter ranging from 1 μηι to 1.00 μι^η, and the subniicroparticles may comprise an average diameter ranging from 1 nm to less than I μτη. In some instances, the micropaiticles may have an. average diameter ranging from 5 μτα to 10 μη . In. some instances, the subniicroparticles may have an average diameter ranging from 85 nm to 220 nm. When, such particles are mixed together, the subniicroparticles cover the outer surface of each of the raicroparticles, forming a template for an inorganic layer (e.g. silica) to be coated thereon. The template is referred to herein as the composite particle. As the submicropartieles cover the outer surface of the microparticles to form the composite particle, the surface-area-to-volume ratio of each mieropariiele is significantly increased. That is to say, the composite particle has a higher surface-area-to-volume ratio compared to the microparticles, even if the microparticles were to be of a single average diameter. The higher surface-area-to-volume ratio in turn improves the amount and quality of inorganic material that is formed onto the composite particle. In various embodiments, each of the composite particles may have a higher surface-area-to- volume ratio than each of the microparticles.

[0055] By using two types of particles having different average diameters, wherein the range of each diameters are as indicated above, a surface-area-to-volume ratio for producing the microparticles wi h the raspberry-like structure may be obtained, according to various embodiments. Such a ratio may provide for improved coating of materials onto the template composite particles.

[0056] On the other hand, when microparticles of a single average diameter or microparticles of low surface-area-to-volume ratio is used as the template particles, the materials to be coated onto the template particles may suffer from low nucleation rate and submicropart eles may form instead of a proper inorganic shell layer coating onto the micron-sized template particles.

[0057] In various embodiments, the microparticles may have an average diameter of 1 μιη to 100 μιτι, 50 μιτι to 100 μπι, 1 μιη to 50 μιη, 5 μηι to 10 μιη, 6 μιη to 10 μηι, 7 pm to 10 μιτι, 8 μηι to 10 μηι. or 9 μιη to 10 μιιι. In certain embodiments, the polystyrene based microparticles may comprise an average diameter of 6 pm or 10 μηι.

[0058] In various embodiments, the submicropartieles may have an average diameter of at least 1 nm but less than l μιτι, 85 nm to 220 nm, 100 nra to 220 ran, 150 nm to 220 nm, or 200 nm to 220 nm. in certain embodiments, the submicropartieles may comprise an average diameter of 85 nra or 220 nm.

[0059] In various embodiments, the microparticles and/or the submicropartieles may be monodispersed or polydispersed. In other words, the microparticles and/or the submicropartieles may be of a uniform diameter or a non-uniform diameter, respectively. [0060] In various embodiments, the microparticles and/or the submicroparticles may be spherical or non-spherical.

[0061] In various embodiments, the microparticles and/or the submicroparticles may be composed of a material selected from a polymer, an inorganic material, or an organic/inorganic hybrid material. In certain embodiments, the polymer may be polystyrene or poly(methyl methacrylate). In certain embodiments, the microparticles may be polystyrene based, microparticles and submicroparticles may be polystyrene based submicroparticles .

[0062] The mixing of the solution comprising microparticles with solution comprising submicroparticles may be carried out to prevent agglomeration between the microparticles, agglomeration between submicroparticles, and/or to spread the microparticles and submicroparticles evenly out in the solution, such that the submicroparticles can evenly cover the outer surface of the microparticles. The mixing may comprise stirring the solution for at least 10 mins, at least 20 mins, at least 30 mi s, etc.

[0063] As already described above, the submicroparticles may be disposed on the outer surface of each of the microparticles. The outer surface, in the context of the present disclosure, refers to the surface of a microparticle on which the submicroparticles can be disposed directly on, i.e. physically in contact with the microparticle. In various embodiments, each of the microparticles and/or submicroparticles may comprise an outer surface which is positively charged, negatively charged or neutral.

[0064] In embodiments where the outer surface of the microparticles is positively charged, the outer surface that is positively charged may comprise -NH₂ functional groups attached to the outer surface. In embodiments where the outer surface is negatively charged, the outer surface that is negatively charged may comprise -COOH functional groups attached to the outer surface. In embodiments where the outer surface is neutral, the outer surface that is neutral may comprise no functional groups attached to the outer surface.

[0065] One example of particles having a positively charged outer surface may include polystyrene-NHa particles. One example of particles having a negatively charged outer surface may include poIystyrene-COOH particles. One example of particles having a neutral outer surface may include polystyrene particles. The particles may refer to microparticles and/or submicroparticles. Such particles may be called polystyrene based microparticles and polystyrene based submicroparticles. The present method is versatile in that the coating of materials, e.g. silica as an inorganic layer, onto the template composite particles, and the formation of the resultant hollow particles, are not adversely affected by the surface charge of the microparticles This is because the high surface-area-to-volurae ratio of the composite particles is able to overcome the effects brought about by the surface charges of the microparticles. For instance, when the microparticles and submicroparticles are both polystyrene-COOH particles, the composite particles can still be formed without any issues for subsequent coating, due to the increased surface-area-to-volume ratio. However, when polystyrene-COOH microparticles of a single average diameter are used, which have low surface-area-to- volume ratio, incomplete silica particle formation occurs, such as not ha ving a complete shell layer, or a mechanically weak shell layer that disintegrates too easily, and/or the resultant particle is formed with a distorted irregular shape.

[0066] In various embodiments, coating the inorganic layer may comprise adding a catalyst to the solution. The catalyst added may depend on. the type of inorganic layer to be coated onto the composite particles. For example, when, silica is to be coated onto the composite particles, the catalyst that is added may comprise ammonium hydroxide. The catalyst is added to aid in the hydrolysis of the inorganic precursor used to form the inorganic layer on each of the composite particles. The formation of the inorganic layer, does not depend on the chemical structure of the catalyst but on the pH instead. Apart from ammonium hydroxide, other basic catalysts such as lithium hydroxide may be used. Acidic catalyst may also be used and examples of such acidic catalyst include hydrochloric acid, perchloric acid, nitric acid, sulfuric acid, formic acid, or acetic acid. In various embodiments, the catalyst may comprise ammonium hydroxide, lithium hydroxide, hydrochloric acid, perchloric acid (HC1.0₄), nitric acid, sulfuric acid, formic acid, or acetic acid.

[0067] After the composite particles are formed, the material to be coated onto the template composite particles can be added to the solution. In various embodiments where the material to be coated is an inorganic material or layer, forming the inorganic layer may comprise adding an inorganic precursor to the solution. The inorganic precursor may be added after adding the catalyst. [0068] In various embodiments, where the inorganic layer comprises silica, gold, silver, or palladium, the inorganic precursor that may be used may comprise a silica precursor, a gold precursor, a silver precursor, or a palladium precursor, respectively. The silica precursor may comprise a silicon alkoxide, or a silicon derivative containing an organic or a polymerizable functional group. "Polymerizable functional group" as used herein refers to an organic functional group which can undergo polymerization to form a polymer. The gold precursor may comprise chloroauric acid (HAiiC ). The silver precursor may comprise silver nitrate. The palladium precursor may comprise potassium tetrachloropall date (II) (K^PdC ).

[0069] In exemplified embodiments where the material to be coated is silica, forming the silica may comprise adding a silica precursor to the solution. The silica precursor may be added after adding the catalyst. In various embodiments, the silica precursor may comprise tetraethyl orthosilicate, or vinyltrimethoxysilane, methyltrimethoxysilane, dimethyldimethoxysilane, (3-aminopropyl)trimethoxysilane, 3-glycidoxypropyltrimethoxysilane, or 3-methacryloxypropyltrimethoxysilane. The silica precursor may comprise tetraethyl orthosilicate or vinyltrimethoxysilane according to certain embodiments. In the presence of ammonia or ammonium hydroxide as the catalyst, the silica precursor undergoes hydrolysis, forming silanol groups and the condensation between the silanol groups creates siloxane bridges (Si- O-Si) forming into silica.

[0070] The solution may be stirred continuously while adding the silica precursor or after adding the silica precursor.

[0071] The composite particles having silica coated/deposited, thereon may be washed and filtered for separation, from the various reactants and residual submicroparticles.

[0072] In various embodiments, the composite particles with the inorganic layer formed thereon, silica layer as an example, may be heated to obtain the resultant particles. That is to say, the composite particles, which are composed from the microparticles and submicroparticles may be burned off or thermally decomposed, leaving behind the coated material, which forms the resultant hollow inorganic microparticles having the raspberry-like structure. In various embodiments, the removal of the composite particles may be carried out by heating the composite particles, wherein removing the composite particles may comprise calcining the composite particles at a temperature of 400°C to 500°C, 450°C to 500°C, or 400°C to 450°C. In certain embodiments, removing the composite particles may comprise calcining the composite particles at a temperature 450°C. Calcining the composite particles may be carried out for 8 to 12 hours, for example, 10 hours.

[0073] In various embodiments, the present method may further comprise drying the composite particles before removing the composite particles. The drying may be carried out via any suitable means known to a person skilled in. die art.

[§074] Various embodiments of the present disclosure also relate to a hollow inorganic microparticle having a raspberry-like structure. The hollow inorganic microparticle having the raspberry-like structure may be obtained or obtainable according to the present method described herein. The hollow inorganic microparticle having a raspberry-like structure may comprise a hollow inorganic microparticle having hollow submicroparticles disposed thereon.

[0075] Various embodiments of the present method, and advantages associated with various embodiments of the present method, as described above, may be applicable to the present hollow inorganic microparticle, and vice versa.

[0076] The hollow inorganic microparticle may be formed from an inorganic layer coated on a composite particle, wherein the composite particle may comprise a microparticle with submicroparticles disposed on the surface of the microparticle. Embodiments regarding the microparticles and the submicroparticles have already been described above. Embodiments regarding the average diameters for the microparticles and submicroparticles have already been described above. Microparticles decorated/covered with submicroparticles on their surfaces form the composite particles, for the inorganic layer coating. The inorganic layer forms on the surfaces of the submicroparticles as well as surfaces of the microparticles that are exposed/not covered by the submicroparticles.

[0077] In various embodiments, the microparticle and the submicroparticle forming the composite particle, which is used as a template for forming the resultant hollow particle, may be polystyrene based, particles for example. The polystyrene based particles are already described above. In various embodiments, the particles may be functionalized with positively charged functional groups, negatively charged, functional groups, or may be non-functionalized (i.e. neutral). Said differently, the outer surface of the particles, the polystyrene based particles for example, may comprise positively charged functional groups (e.g. -NH₂). negatively charged functional groups (e.g. -COOH), or no functional groups (i.e. neutral).

[0078] In various embodiments, the microparticies and submicroparticles, forming the composite particles, which are used as a template for forming the resultant hollow inorganic particle, may be made from other types of polymer, such as poly(methyl methacrylate) (PMMA), an inorganic material, or an. organic/inorganic hybrid materials.

[0079] The composite particle may be removed after coating the material (e.g. silica) by, for example, heating. The removing may be achieved by calcination. Once the template composite particles are removed, the inorganic layer coating remains to form the resultant hollow inorganic microparticies each having the raspberry-like structure.

The composite particle may also be removed by dissolution, for example dissolving in organic solvents for composite particles made of polymers, or by acidic or basic etching for composite particles made of inorganic materials, or the combination of the two for organic/inorganic hybrid materials. This may be applied to various embodiments of the present method described above.

[0080] In various embodiments, the hollow microparticle and the hollow submicroparticles may be formed as a single entity. In such an entity, the submicroparticles may partially or entirely cover the hollow microparticle. Said differently, there may be a variable coverage of the hollow submicroparticles on the hollow microparticle.

[0081] The hollow microparticle may comprise a diameter ranging from 1 pm to 100 pm, 50 μπι to 100 pm, 1 μηι to 50 pm, 5 μηι to 10 μηι, 6 pm to 10 μηι, 7 μιη to 10 μηι, 8 pm. to 10 pm., or 9 pm to 1.0 pm. In some instances, the hollow microparticle may have a diameter ranging from 5 pm to 10 pm. In certain embodiments, the hollow microparticle may comprise a diameter of 6 pm or 10 pm.

[0082] In various embodiments, each, of the hollow submicroparticles may have a diameter of at least I nm but less than 1 pm, 85 nm to 220 nm, 100 nm to 220 nm, 150 nm to 220 nm, or 200 nm to 220 nm. In some instances, each of the hollow submicroparticles may have a diameter ranging from 85 nm to 220 nm. In certain embodiments, each of the hollow submicroparticles may comprise a diameter of 85 nra or 220 nm.

[0083] In various embodiments, the hollow niicroparticle and/or the hollow submicroparticles may be monodispersed or polydispersed.

[0084] In various embodiments, the hollow microparticle and/or the hollow submicroparticles may be spherical, substantially spherical or non-spherical.

[0085] In various embodiments, the hollow inorganic niicroparticle may be composed of silica, gold, silver, or palladium.

[0086] In various embodiments, the hollow inorganic microparticle may comprise a mcsoporous shell formed from the hollow submicroparticles. The term "mesoporous" as used herein refers to a material having pore diameters ranging from 2 nm to 50 nm.

[0087 ] In summary, the present method involves a simple step of mixing micron- sized and submicron-sized particles, which are used to promote coating of materials (e.g. silica) onto the micron-sized particles to form hollow inorganic microparticles having an average diameter in. the micrometer range.

[0088] The present method may involve simple mixing between micron-sized particles of any surface charge and negatively charged submicron-sized particles to form hierarchical composite templates for inorganic material coating The hierarchical composite templates, as compared to micron-sized particles when used alone, have higher suiface-area-to-volume ratio, which significantly enhances the formation of the inorganic layer on the template particles, covering the entire of each template particle. The removal of the template particles by calcination forms the micron-sized hollow core-shell particles. The straightforward mixing in the present method renders the present method much easier over all other conventional methods, as no covalent bonding or surface modification is required. The present method advantageously allows for particles bearing the same surface charges to be mixed to obtain the hierarchical composite templates through such simple mixing.

[0089] The present method is also advantageous as it utilizes the surface-area-to- volume ratio of the template composite particles for controlling the coating of inorganic materials onto the template composite particles.

10090] The resultant hollow inorganic microparticles may be 6 μηι or 10 ,um, and they may have a hierarchical submicroHS-on-microHS raspberry-like structures with both submicroHS and microHS each having a narrow size distribution, and the coverage of the submicroHS varies from low to high. The resultant particles, as compared to conventional microbeads, are superior at least in the following aspects: (i) made of an inert material (e.g. silica), (ii) narrow size distribution in the micrometer size range, (iii) low density, (iv) have a unique raspberry-like morphology with variable coverage of submicroSHS on. raicroSHS, (v) may have hollow spaces in. microSHS, submicroSHS and mesopores, wherein the entire raspbery-like resultant particle, including the shell of the microHS and the shell of the submicroHS, are mesoporous having a mesopore size range of between 2 and 50 run. (vi) have a higher surface area, and (iv) have sizes are controllable based on the microparticles and submicroparticl.es used.

[0091] In the context of various embodiments, the articles "a", "an" and "the" as used with regard to a feature or element include a reference to one or more of the features or elements.

[0092] In the context of various embodiments, the term "about" or "approximately" as applied to a numeric value encompasses the exact value and a reasonable variance.

[0093] As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.

[0094] Unless specified otherwise, the terms "comprising" and "comprise", and grammatical variants thereof, are intended to represent "open" or "inclusive" language such that they include recited elements but also permit inclusion of additional, unrecited elements.

[0095] While the methods described above are illustrated and described as a series of steps or events, it will be appreciated that any ordering of such steps or events aire not to be interpreted in a limiting sense. For example, some steps may occur in different orders and/or concurrently with other steps or events apart from those illustrated and/or described herein, in addition, not all illustrated steps may be required to implement one or more aspects or embodiments described herein. Also, one or more of the steps depicted herein may be carried out in one or more separate acts and/or phases. Examples

[0096] The present disclosure provides for a method of synthesizing micron-sized hollow spheres (microHS), such as micron-sized silica, hollow spheres (microSHS ). The present method is straightforward, versatile and easy to scale.

[0097] The present method is advantageously versatile as it can be applied to synthesis of raspberry-like micron-sized particles made of any other materials as long as the synthesis reaction involves precursor hydrolysis and condensation of the inorganic network on a hard template. For example, raspberry-like micron-sized particles made of gold, silver, or palladium, can be produced using the present method with HAuC , AgNOs, or K^PdCU as the respective inorganic precursor.

[0098] The present disclosure also provides for such microHS. The hollow spheres may be termed hierachical hollow spheres as such hollow spheres are structurally configured such that various submicron-sized hollow spheres (submicroHS) are disposed on one or more microHS, giving rise to a raspberry-like structure. This renders the hollow spheres unique in size, surface morphology and surface properties, such as high surface area.

[0099] The terms "sphere" and "particle" may be used interchangeably in the context of the present disclosure.

[00100] The present method and resultant particles, as mentioned above, are described by way of non-limiting examples, as set forth below.

[00101] Example 1: Materials

[001021 Tetraethyl. orthosiiicate (TEOS, 98%) and vmyltrimethoxysilane (VTMS, 98%) from Sigma-Aldrich, ammonia solution (NH₄OH, 28-30%) from Merck, and ethanol (HPLC grade, 99.99%) from. Fischer, were all used as received without further purification.

[00103] The following polymeric spheres were purchased from Polysciences in the form of 2.5 weight/volume percent (w/v%) solids aqueous suspensions, and each type of these polymeric spheres was based on average diameters of 6 μπι and 10 μηα for microspheres, or 85 11m for nanospheres. That is to say, for example, where one type of microspheres was purchased, they were in. average diameters of 6 μηι and 10 pm, separately. The polymeric spheres include, but are not limited to, polystyrene (PS) microspheres and nanospheres, plain PS microspheres (Polybead® polystyrene microspheres, without surface functional groups), PS-NH₂ microspheres (Polybead® amino microspheres, with surface primary amine groups) and PS-COOH microspheres (Polybead® carboxylate microspheres, with surface carboxyi groups). Additionally, PS-COOH paiticies with an average diameter of 220 nm in the form of 10 weight percent (wt%) aqueous suspension were purchased from Bangs Laboratories. All particles (i.e. spheres) were washed three times with distilled water, and resuspended in distilled water at various concentrations before use.

[00104] Example 2A: Hard-Templating Method Using Particles of a Single Average Diameter as Hard Templates

[00105 ] Polystyrene (PS) particles of a single average diameter were used as the hard templates. TEOS or VTMS was used as the silica precursor. Parameters such as amount of NH4OH (associated with the reaction pH), amount of TEOS or VTMS, amount of templating paiticies can be varied. The conditions applied are described in examples 2B and 2C.

[00106] Example 2B: Hard-Templating Method Using PS Based Particles with Average Diameter of 220 nm as Hard Templates

[00107] Modified stober method using VTMS as the silica precursor was adopted to generate mesoporous silica. This method is described as follows.

[00108] 100 pL of VTMS was added into 2.21 ml . of distilled water under vigorous magnetic stirring for 30 mins to form a. transparent solution. Simultaneously, 5 mL of

220 nm PS-COOH (0.5 wt%) water dispersion was mixed with 300 pL of NH₄OH under magnetic stirring for 15 mins. To the latter mixture, the former VTMS solution was added dropwise and the reaction was stirred for 6 hrs at room temperature (30 ± 10 °C).

The templating particles were then separated from the other reactants by centrifugation at 9000 rpm for 15 mins, washed five times with ethanol and three times with, water, and suspended in distilled water before thermal removal of the PS hard templates.

[00109] Example 2C: Hard-Templating Method Using PS Based Particles with

Average Diameter of 6 urn as Hard Templates

[0011 ] in this method, when PS-COOH microspheres were used as the templates, VTMS was used as silica precursor with the following conditions: 20 pL of VTMS was added into 663 pL of distilled water under vigorous magnetic stirring for 30 mins to form a transparent solution. Simultaneously, 150 pL of 6 pm (average diameter) PS- COOH (0.5 w/v% solids) water dispersion was mixed with 150 pL of NH₄OH under magnetic stirring for 15 niins. To the latter mixture, the former VTMS solution was added dropwise and the reaction was stirred for 14 hrs at room temperature (30 ± 10 °C). The microspheres were then separated from the other reactants by centrifugation at 3000 rpm for 10 mins, washed five times with ethanol and three times with water, and suspended in distilled water before thermal removal of the PS hard templates.

[00111] In this method, when PS or PS-NH2 microspheres were used as the templates, TEOS was used as silica precursor with the following conditions: 75 pL of 6 μηι PS or PS-NH2 microspheres (2.5 w/v% solids) were mixed with 1.15 ml, of ethanol under magnetic stirring, and 100 μΐ, of NH4OH and 20 pL of TEOS were then added to the reaction mixture, and the reaction was allowed to proceed at room temperature (30 ± 10 °C) for 14 hrs under constant stirring. Finally, the microspheres were separated from the other reactants by centrifugation at 3000 rpm for 10 mins, washed five times with ethanol and three times with water, and suspended in distilled water before thermal removal of the PS hard temp] ates .

[00112] Example 3A: Hard-Templating Method Using A Mixture of Micron-sized and Submicron-sized Particles as Hard Templates

[00113] Micron-sized hard templates were mixed with submicron-sized particles to allow interactions between them and then subjected to silica coating and template removal.

[00114] Example 3B: Hard-Templating Method Using A Mixture of PS based Micron, and PS based Submkron Particles

[00115] 1 niL of 6 μηι PS-COOH microspheres, 6 μιη PS-NH₂ microspheres, 6 pm PS microspheres, or 10 μηι. PS-COOH microspheres (2.5 w/v% solids), was mixed with 4 nil., of 85 nm or 220 nm PS-COOH (0.5 wt%) particles under constant stirring for 30 mins. The dimensions indicated refer to the average diameter of the particles.

[00116] Afterwards, 300 pL of NH4OH was added into the mixture under magnetic stirring and the solution was stirred for another 15 mins. A transparent diluted VTMS solution, was prepared with 100 pL of VTMS added into 2.21 niL of distilled water under vigorous magnetic stirring for 30 mins. This diluted VTMS solution was then added dropwise to the mixture and the reaction was stirred for 6 hrs at room temperature (30 ± 10 °C). All particles were then, separated from the other reactants by centrifugation at 9000 rpm for 15 mins, washed five times with ethanol and three times with water and suspended in distilled water. Finally, microspheres were further separated from submicron particles by using Durapore® hydrophiiic polyvinylidcne difluoride (PVDF) membrane filters with pore size of 5 μηι at 5000 rpm for 5 mins for five times before thermal removal of the PS hard templates.

[00117] Example 4; Removal of Hard Templates

[00118] After silica coating, hard templates dispersed in distilled water were transferred into glass vials, dried in a 65 °C oven, then calcined in a muffle furnace at 450 °C (ramp rate: 2 °C/min) for 10 hrs in air before they were slowly cooled down to room, temperature. After calcination, samples were dispersed in water and sonicated for 6 hrs before SEM and TEM characterizations.

[00119] Example 5: Characterization

[00120] Scanning Electron Microscopy (SEM): samples were drop cast on clean silicon wafer, dried and coated with gold using JEOL JFC-1300 coater operated at 10 mV for 20 sec. SEM images were obtained using field emission scanning electron, microscopy (FES EM) JSM6700F operated at .1.0 kV.

[00121] Transmission Electron Microscopy (TEM): samples were drop cast onto TEM copper grids and TEM images were acquired using high-resolution transmission electron microscopy (HRTEM) Philips CM300 FEGTEM operated at 300 kV.

[00122] Example 6A: Results and Discussion - Schematic Comparison of Conventional Hard-Templating Method and Present Method

[00123] FIG. I A illustrates the conventional, hard-templating method while FIG. IB illustrates the hard-templating method of the present disclosure. The latter is developed for synthesis of silica hollow spheres (SHS), as an example. In the conventional method as shown in FIG. l A, particles of a single average diameter, e.g. polystyrene (PS) nanospheres or microspheres, are used as the hard templates for silica coating, which are then removed, for example, by calcination to produce the SHS. Such conventional method may be used to produce submicron-sized SHS (submicroSHS). However, when the conventional method is used with micron-sized templates, problematic silica shells such as distorted shapes and even incomplete SHS were produced (also see FIG. 3A to 3F). the present hard-templating method (see FIG. 1 B) has been developed to overcome such challenges and synthesize microSHS. [00124] For the present method, only a simple mixing of the micron-sized and submicron-sized particles is required before silica coating to produce uniform-sized SHS in the micrometer size range. The resultant SHS have a submicroSHS-on- microSHS raspberry-like structure with variable coverage of submicroSHS (low to high) on the microSHS.

[00125] Example 6B: Results and Discussion - Conventional Hard-Templating Method

100126] Conventional hard-templating method was first used to produce SHS. When PS-COOH particles having an average diameter of 220 nm were used as the hard templates, uniform-sized submicroSHS with a diameter of 200 ± 2 nm were successfully produced with uniform shell thickness of 25 ± 2 nm (FIG. 2). The shell thickness here provides good mechanical strength to the submicroSHS, rendering them intact even after centrifngation at 9000 rpm and 6 hrs sonication. A thicker or thinner shell can be achieved by changing reaction conditions such as H, amount of silica precursor or reaction time.

[00127] In contrast, when micron-sized templates such as PS microspheres having an. average diameter of 6 fim were used as the hard templates, conventional hard- templating method failed to produce intact SHS even after optimization of reaction conditions such as pH, amount of silica precursor or reaction time. This demonstrates that conventional hard-templates cannot be adopted for micron-sized templates simply based on how it works with submicron-sized templates.

[00128] FIG. 3A to 3F show the TEM images of silica shells synthesized using microspheres having average diameter of 6 μηι as the hard templates. Though microspheres with negative surface charges, positive surface charges and neutral surfaces, e.g. PS-COOH (FIG. 3A and 3B), PS-NH? (FIG. 3C and 3D) and PS (FIG. 3E and 3F) microspheres, respectively, were all tested, none of them produced, the structure as shown in FIG. 2.

[00129] The silica coating on hard templates may be strongly affected by the size as well as surface charge of the templating particles. Thus, micron-sized templating particles having an average diameter of 6 μιιι, with negative surface charges (PS- COOH), positive surface charges (PS- NH₂) and neutral surface (PS, without surface functional groups), were used as hard templates for silica coating. The negative surface charge of PS-COOH microspheres could present repulsive force towards the negatively charged silica sol thus hindering its deposition onto the templating particles' surface, resulting in very thin silica shell of non-uniform thickness (FIG. 3A and 3B). Such micron-sized silica shells easily deform to a distorted shape (FIG. 3A) or have their shell easily broken due to lack of the shell's mechanical strength to endure treatment such as centrifugation, washing and/or son i cat ion before characterization.

[00130] When PS~NH₂ microspheres were used as the hard templates, the attractive force between the positively charged surface groups on PS~NH₂ microspheres and the negatively charged silica sol could facilitate the deposition of silica onto the templating beads. Silica nuclei first, formed on the surfaces of PS-NH₂ templating particles through random, collision, which then further grew into thin silica shell. However, due to the low surface-area-to-volume ratio of the micron-sized templating particles, the silica nucleation rate was low and the growth rate of silica surpassed the nucleation rate, resulting in silica submicroparticles, instead of hollow silica spheres, deposited on the templating particles and co-produced with the silica shells. During calcination, silica submicroparticles self-assembled into micron-sized aggregates and these aggregates were very difficult to be separated from the silica shells (FIG. 3C and 3D).

[00131] When using neutrally charged PS templating particles, there could be a weak, attractive interaction between the organic core templates and the inorganic silica species due to van der Waals forces or hydrogen bonding. Such interactions could facilitate the assembly of silica onto the templating particles to form silica shells and also lots of individual, silica submicroparticles, instead of hollow silica spheres (FIG. 3E and 3F). These observations showed mat surface charges of the hard templates play only minor roles in controlling the nucleation and growth of the silica shells and the morphology of the deposited silica coating.

[00132] Comparing results of FIG. 2 and FIG. 3A to 3F, submicroSHS with complete shell and uniform shell thickness were successfully templated using 220 nm PS-COOH particles as the hard templates (FIG. 2) but SHS in micrometer size range could not be synthesized using PS-COOH, PS-N¾ or PS templating particles having an average diameter of 6 μηι (FIG. 3A to 3F) even after ^'tuning of various reaction parameters as mentioned above. The clear size difference of the hard, templates led to a comparison of their surface-area-to-volume ratios, and the surface-area-to-volume ratio of the individual 6 μ ι templating microspheres was about 1/27 of that of the 220 nm templating particles. These results suggest that surface-area-to-volume ratio of the hard templates has a considerable effect on the silica coating of the hard templates.

[§§133] The effect from, the surface-area-to- volume ratio of the hard templates explains why most conventional SHS synthesized from hard templates were in the submicrometer range and at most 1 μιη. Conventionally, SHS above 1 μιη were templated from soft templates but they were not uniform in size because soft templates are very sensitive to reaction environment and have a wide range of size distribution and also difficult to reproduce and scale up.

[00134] Example 6€: Results and Discussion - Present Hard-Templating Method

[00135] The present method provides for low cost way of synthesizing uniform sized SHS in the micrometer size range. Compared to conventional hard-templating method, the present method involves one simple step before silica coating, which is the mixing of micron-sized hard templates with submicron-sized particles (FIG. IB). This step allows the decoration of the micron-sized hard templates with the submicron-sized particles so as to increase the surface-area-to-volume ratio of the hard templates for effective silica coating. To demonstrate this, microspheres with an average diameter of 6 μηι. and 10 μιη, and particles of 85 nm and 220 nm, were used as the micron-sized and submicron-sized hard templates, respectively.

[00136] First, microspheres having an average diameter of 6 μπι with different surface charges, e.g. PS-COOH. PS-NH2 and PS were used to test the versatility of the present hard-templating method by mixing them with 220 nm particles before silica coating. SEM was used to visualize the surface morphology of the microspheres before and after the mixing as an indicator of the change in surface area. As the volume of one 220 nm sphere is 4.93 x HY^:' of the volume of one 6 pm microsphere, the change in surface area of the microspheres can. be used to understand the change in their surface-area-to- volume ratio. FIG. 4 shows the surface morphology of the 6 μ m microspheres before (Fig. 4A, 4C & 4E) and after (Fig. 4B, 4D & 4F) mixing with 220 nm PS-COOH particles. It can be seen that before mixing, the commercially available PS-COOH microspheres (average diameter of 6 μηι) have a rough surface morphology (FIG. 4A) and both the 6 pm PS-NH2 and PS microspheres have smooth surface morphology (FIG. 4C and 4E). After mixing with 220 nm PS-COOH particles and also washing to remove the excess 220 lira particles (three times, in Dl water, 1000 rpm, 5 mins per wash), all of the 6 μηι PS-COOH, PS-NHi and PS microspheres, regardless of their surface charges were decorated with 220 nm PS-COOH particles on their surfaces (FIG. 4B, 4D and 4F). This attachment of the 220 nm particles onto the microspheres could be due to electrostatic interaction between oppositely charged particles and weak Van der Waals interaction or columbic repulsion between identically charged particles and also between neutrally and negatively particles.

[00137] Comparing FIG. 4B, and FIG. 4D and 4F, there were more 220 run particles attached on the PS-COOH microspheres. This could be due to the difference in surface morphology when comparing the PS-COOH microspheres (FIG. 4A) with PS-NH₂ and PS microspheres (FIG. 4C and 4E). From. FIG. 4B, FIG. 4D, and FIG. 4F, it can also be seen that distribution of the 220 nm particles attached on the microspheres was quite even and there were clusters of self-assembled 220 nm particles attached onto the microspheres. Conventional studies on attachment of silica, gold or PS subm!croparticles onto PS microparticles demonstrated that the number of binding si tes may be limited by the net charge of the PS microparticles and the electrostatic double layer or columbic repulsions among the submicroparticles. When, nanospheres and microspheres were mixed in water, nanospheres could be attracted into the electrostatic double layer of the microspheres and may thus be regarded as multivalent, counterfoils of the microspheres. These nanospheres could be mobile along the surface of the microspheres and attached in an evenly spread out manner on the microsphere surfaces. As the double layer repulsions among nanospheres are less strong when located within the double layer of microspheres than in the bulk solution, nanospheres could assemble into clusters and attach onto the microspheres.

[00138] Mixing of micron-sized particles with submicron -sized particles allowed interactions between them and decoration of the small particles onto the big particles, producing micron-sized hierarchical templates with submicron particles on micron particles, resulting in raspberry-like morphology (FIG. 4B, FIG. 4D and FIG. 4F). These templates, when compared with the use of micron-particles alone, presented bigger surface-area-to-volume ratio. When reactants for silica coating were introduced into the particle mixture, deposition of silica onto the micron-sized hierarchical templates could start, and during the silica coating process, more submicron-sized particles in. the reaction mixture could attach onto the micron-sized templates, rendering it favorable for continuous growth of the silica coat. After template removal via calcination, the final SHS structures were characterized with TEM and shown in FIG. 5B, FIG. 5D and FIG. 5F. The top panel (FIG. 5 A and 5B) are SHS tempiated from the micron-sized templates in FIG. 4B, which utilized a mixture of 6 pm PS-COOH microspheres with 220 nm PS-COOH particles. The middle panel (FIG. 5C and 5D) are tempiated from the templates in. FIG. 4D, whic utilized 6 pm PS-NEb microspheres mixed with 220 nm PS-COOH particles. The lower panel (FIG. 5E and 5F) are from templates in FIG. 4F, which utilized 6 μηα PS microspheres mixed with 220 nm PS- COOH particles. Images on. the left panel (FIG. 5A, FIG. 5C and FIG. 5E) are of lower magnification showing the entire microSHS structures while images on the right panel (FIG. 5B, FIG. 5D and FIG. 5F) show the magnified surfaces of the respective SHS.

[00139] It can be clearly seen that hierarchically organized raspberry-like structures, intact micron-sized SHS decorated with intact submicron-sized SHS, were successfully obtained using PS microspheres mixed with PS submicron-particles as the hard templates (method illustrated in FIG. I B). It is worth noting that from the lower- magnificatio images (FIG. 5 A, FIG. 5C and FIG. 5E), the as-obtained micron-sized hierarchically organized structures exhibited no obvious difference in terms of dimension or morphology when microspheres (average diameter of 6 μιη) with different surface functional groups (e.g. with carboxylate PS-COOH in FIG. 5A, with primary amine groups PS-NHi in FIG. 5C) or without any surface functional groups (PS in FIG. 5E), mixed with the same 220 nm. PS-COOH particles were used as the hard templates.

[00140] Based on the magnified surfaces of the microSHS with raspberry-like structures, as shown, in FIG. 5B, FIG. 5D and FIG. 5F, a difference in. morphology can. be observed between the raspberry-like structures obtained using PS-COOH microspheres (FIG. 5B) and those obtained from. PS-N¾ (FIG. 5D) or PS microspheres (FIG. 5F). In FIG. 5B, it can. be seen that the surface of the raspberry-like structures shown in FIG. 5A consists of submicroSHS of uniform size together with small amount of amorphous silica. Meanwhile, from FIG. 5D and FIG. 5F, the surfaces of the raspberry- like structures shown in FIG. 5C and FIG. 5E consist of uniform submicroSHS only. This difference might be due to the interaction between the PS- COOH microspheres and PS-COOH submicron-particles, where hydrogen bond formation between these particles might have played a role in the form of hydronium ion, which could lead to deposition of small amount of silica on the template surfaces.

[00141] The uniform submicroSHS on the surfaces of all the raspberry-like structures show a size of around 200 nm with shell thickness of about 20 run. These submicroSHS were templated from the submicron-particles in the mixture. It is to note that from all three sets of particle mixtures, the structures of the micron-sized templates were retained, that is to say, no distorted hollow structures or incomplete silica shells as shown in. FIG. 3B and FIG. 3D were produced.

[00142] The results shown in FIG. 4A to 4F and FIG. 5.A to 5F demonstrated that the present hard-templating method is versatile as it can be applied to micron-sized particles of any surface charges. Even when negatively charged PS-COOH microspheres were used to mix with negatively charged PS-COOH submicron-particles, a good coverage of submicron-particles on the surface of the microspheres were observed (FIG. 4B), and after silica coating and template removal, intact microSHS with raspberry-like structure were obtained (FIG. 5A). The as-synthesized microSHS (FIG. 5 A, FIG. 5C and FIG. 5E) are mechanically strong and physically stable because they survived various sample treatment procedures such as calcination, sonication, centrifugation, etc.

[00143] The present hard-templating method also offers tunability in the dimensions of the microii-and submicron-hollow compartments of the hierarchical SHS structure because the micron-sized hollow compartments are templated from the micron-sized particles and the submicron-sized hollow compartments are templated from the submicron-sized particles. To demonstrate this tunability, microspheres having average diameter of 6 μηι and microspheres having average diameter of 10 μιη, and submicron- particles of 220 nm and 85 nm, were used. FIG. 6A shows the SHS obtained from mixing 6 μ m PS-COOH microspheres with 85 nm PS-COOH particles and FIG. 6C shows the SHS templated from mixing 10 μιη PS-COOH microspheres with the 220 nm PS-COOH particles. FIG. 6B and FIG. 6D are the respective higher resolution images for the structures of FIG. 6A and 6C. It can be clearly seen that intact SHS with microSHS of 6 μηι decorated with submicroSHS of 80 nm were obtained in FIG. 6A and FIG. 6B while intact SHS with 10 μηι microSHS decorated with 200 nm. submicroSHS were produced as shown in FIG. 6B and FIG. 6D. The successful synthesis of SHS with tunable sizes demonstrates that the present hard-templating method is also versatile in terms of the te.mplati.ng particles of different sizes. The coverage of the submicroSHS on microSHS in FIG 6A seems less than that in FIG. 6C but in both cases intact microSHS were obtained despite the coverage of the submicroSHS. This may be useful, where low coverage is desired, as conventional microSHS tend to be produced with a high coverage of more than 80% of submicroSHS. This could be due to the increased efficiency of silica deposition onto the whole hierarchical construct due to the increased surface-area-to-volume ratio of the hard templates after mixing the particles.

[00144] To show surface morphology of the SHS, microSHS templated from 6 pm PS- COOH microspheres mixed with 220 nm PS-COOH particles were imaged under SEM and the low and high magnification images are shown in FIG. 7 A and FIG. 7B, respectively. The SEM image of FIG. 7 A and FIB. 7B are in good agreement with the TEM images in FIG. 5A to FIG. 5F, showing clear raspberry-like structures.

[00145] Exampte 61); Results and Discussion - Summary

[00146] In. conclusion, the present hard-tem.plati.ng method provides for synthesis of uniform microSHS. This method is very simple, involving only mixing of micron-sized hard templates with submicron-sized particles before silica coating (FIG. I B). Without this mixing, conventional hard-templating method could produce mostly submicroSHS or microSHS not more than 1 pm (FIG. 2). The conventional method also fails to produce big microSHS even though micron-sized hard templates of different surface charges were tested (FIG. 3A to FIG. 3F). After this mixing step, micron-sized hard templates were all decorated with submicron-sized particles on their surfaces (FIG. 4A to FIG. 4F), resulting in increased surface-area-to-volume ratio, and after template removal, uniform SHS (e.g. average diameter of 6 pm. average diameter of 10 pm) were successfully synthesized with submicroSHS-on-niicroSHS raspberry-like morphology (FIG. 5 A to FIG. 5F and FIG. 6A. to 6.D) regardless of the coverage of the submicroSHS. This method is very versatile because (i) micron-sized particles with any surface charge, negative, neutral or positive can all be used (FIG. 5 A to FIG. 5.F), (ii) the sizes of the microSHS and submicroSHS in the raspberry-like structure can be easily tu ed by changing the sizes of the micron-sized and submicron-sized particles, respectively (FIG. 6A to FIG. 6D), and. (iii) the hierarchical SHS can be successfully synthesized with variable coverage of submicroSHS. The present hard-templating method can be potentially applied for coating of materials apart from silica, such as silver or gold, onto micron-sized hard templates to produce micron-sized silver or gold hollow spheres. Additionally, microSHS as a group of new materials which have distinctive SHS properties are successfully synthesized. Such properties include: (1) uniform size in a few micrometer size range, (2) unique raspberry-like morphology with variable coverage of submicroSHS on microSHS, (3) low density and large loading capacity owing to the hollow space in. microSHS, submicroSHS and the mesopores, (4) huge surface area because of the submicroSHS o the surfaces and the mesoporous nature of the material, and (5) controllable sizes in both micron-and submicron-scales. These properties provides for a new range of applications for the present microSHS, which include but are not limited to, use as a microbead platform for bead-based detections because (a) their hydroxy! surface groups and high surface areas allow easy modification of high density surface functional groups or molecules, (b) their low density renders them more suspendable in solutions for better reaction efficiency as compared with their non-hollow counterparts, (c) the inertness of silica allows the use of the beads in organic solvents and inorganic dispersants of various H, and (d) their micrometer size makes them easily imaged with optical microscopes and manipulated with centrifugal washing or microfluidic patterning. Also, these SHS can be used to load chemicals or submicroparticles in microSHS, submicroSHS and mesopores for delivery. They can be applied directly onto surfaces as a form of coating to introduce both micron-and. submicron-scale roughness together with other properties if loaded wi th submicroparticles.

[00147] Example 7: Advantages of the Present Method and Present Hollow Particle

[00148] The present method of synthesizing hollow inorganic in.icroparti.cl.es with raspberry-like structures may, for example, comprises:

[00149] mixing a solution comprising hard templating particles in the micrometer size range with hard templating particles in the submicrometer size range to form composite particles each comprising one micrometer-sized, particle having plurality of submicrometer-sized particles disposed thereon, forming silica, as an example, on each of the composite particles, and removing the composite particles to obtain, the hollow silica particles. [§0150] The composite particles have higher surface-area-to-volume-ratio as compared with the micrometer-sized particles without subnucrometer-sized particles disposed thereon. The surfece-area-to-volume-ratio of the hard templates is a key parameter in the present hard tempi ating method.

[00151] The micrometer-sized particles suitable for the present method can be of any surface charge: positive, negative or neutral.

[00152] The micrometer-sized particles and submicrometer-sized particles suitable for the present method can. be of any shape, spherical or non-spherical.

[00153] The micrometer-sized particles and submicrometer-sized particles suitable for the present method can be of any material, polymer, such as polystyrene or poly(methyl methacrylate) (PMMA), an inorganic material, or an organic/inorganic hybrid materials.

[00154] The micrometer-sized particles suitable for the present method can be any size ranging from 1 μπι to 100 μιη, and the submicrometer-sized particles suitable for the present method can be any size ranging from at least 1. nrn to less than 1 μηι.

[00155] The present method can be applied to synthesis of raspberry-like micron-sized, particles made of any other materials as long as the synthesis reaction involves precursor hydrolysis and condensation of the inorganic network, on. a hard template. For example, raspberry-like micron-sized particles made of gold, silver, or palladium, can be synthesized using this method with HAuCl₄ , AgN0₃ or K PdCL, as the respective precursors.

[00156] The raspberry-like hollow particles synthesized via the present method are particles having one micrometer-sized hollow particles with plurality of submicrometer-sized hollow particles disposed thereon. The micrometer-sized hollow particles and the plurality of the submicrometer-sized. hollow particles are synthesized as one complete structure having raspberry-like appearance. The coverage of the submicrometer-sized hollow particles on the micrometer-sized hollow particles is variable.

[00157] The size of the micrometer-sized hollow particle in the raspberry-like particle can be from 1 μηι to 1.00 μηι and the size of the submicrometer-sized hollow particles in the raspberry-like particle can be from 1 nm to less than 1 μιη. The size of the micrometer-sized hollow particles in the raspberry-like particle can be uniform or non- uniform. The size of the submicrometer-sized hollow particles in the raspberry-like particle can be uniform or non-uniform. The size of the micrometer-sized hollow particle in the raspberry-like particle can be controlled from. 1 μτη to 100 μηη; and the size of the submicrometer-sized hollow particle in the raspberry-like particle can be controlled from 1 nni to less than I μιη.

[00158] The shape of the micrometer-sized hollow particles and the submicrometer- sized hollow particles in the raspberry-like particle can be spherical or non-spherical.

[00159] The raspberry-like particles have hierarchical hollow spaces, in the niesopores of the shell structures, in the submicrometer-sized hollow particles and the micrometer- sized hollow particles.

[00160] The raspberry-like particles can be made of silica, gold, silver, palladium, etc.

[00161] Example 8: Commercial and Potential Applications

[00162] The resultant particles may be used as a microbead platform for sensing applications. They may also be used in low-density applications e.g. ultrasound imaging agents. The resultant particles, when coated with silica, may be used to form a superhydrophobic coating. The resultant particles may be used as agents for drug loading and delivery, in energy storage and generation applications, as catalysts or carriers for catalysts, for heavy metal ion separation, or applications that involve surface roughness-regulated cell interactions. The resultant particles are particularly suitable for applications that require particles in the micrometer size range, e.g. 5 μτα to 10 μιτι, having a good size uniformity, have high surface-area-to-volume ratio, low density, hollow core, and/or composed of inert materials.

[00163] While the invention has been particularly shown and described with reference to specific embodiments, it should be understood by those skilled in the art that various changes in form and detail may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. The scope of the invention is thus indicated by the appended claims and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced.

Claims

1. A method of synthesizing hollow inorganic microparticles each having a raspberry-like structure, the method comprising:

mixing a solution comprising microparticles and submicroparticles to obtain composite particles, wherein each of the composite particles comprises one mieroparticle having the submicroparticles disposed thereon;

forming an inorganic layer on each of the composite particles; and

removing the composite particles to obtain the hollow inorganic microparticles each having the raspberry-like structure.

2. The method of claim 1 , wherein the microparticles and/or the submicroparticles do not require surface modification.

3. The method of claim 1 or 2, wherei each of the composite particles has a higher surface-area-to-volume ratio than each of the microparticles.

4. The method of any one of claims 1 to 3, wherein each, of the microparticles comprises an outer surface which is positively charged, negatively charged or neutral.

5. The method of claim 4, wherein the outer surface which is positi vely charged comprises -NH₂ functional groups attached to the outer surface.

6. The method of claim 4, wherein the outer surface which is negatively charged comprises -COOH functional groups attached to the outer surface.

7. The method of claim 4, wherein the outer surface which is neutral comprises no functional groups attached to the outer surface.

8. The method of any one of claims 1 to 7, wherein the inorganic layer comprises silica, gold, silver, or palladium.

9. The method of claim 8, wherein, the inorganic layer is formed from an inorganic precursor comprising a silica precursor, a gold precursor, a silver precursor, or a palladium precursor.

10. The method of claim 9, wherein the silica precursor comprises a silicon alkoxide, or a silicon derivative containing an organic or a polymerizable functional group.

11. The method of claim 9 or 10, wherein, the silica precursor comprises tetraethyl orthosilicate, vmyltrirnethoxysilane, metliyltrimethoxysilane, dimethyldimefhoxysilane, (3-aminopropyl)trimethoxysilane, 3- glycidoxypropyltrimcthoxysilarie. or 3-methacryloxypropyltrimethoxysilane.

12. The method of claim. 9, wherein the gold precursor comprises chloroauric acid.

13. The method, of claim 9, wherei n the silver precursor comprises silver nitrate.

14. The method of claim 9, wherein the palladium precursor comprises potassium, tetrachloropalladate (II) .

1.5. The method of any one of claims 1 to 1.4, wherein each of the microparticles comprises an average diameter ranging from 1 μηι to 100 μηι.

16. The method of any one of claims 1. to 15, wherein each of the submicroparticles comprises an average diameter ranging from 1 nm to less than 1 μιη.

17. The method of any one of claims 1 to 16, wherein, the microparticles and/or the submicroparticles are monodispersed or polydispersed.

18. The method of any one of claims 1 to 17, wherein the microparticles and/or the submicroparticles are composed of a material selected from a polymer, an inorganic material, or an organic/inorganic hybrid material.

19. The method of claim 18, wherein the polymer is polystyrene or poly(methyl methacrylate).

20. The method of any one of claims 1 to 19, wherein the microparticles and/or the submicroparticles are spherical or non-spherical.

21. A hollow inorganic microparticle having a raspberry-like structure, wherein the hollow inorganic microparticle comprises a hollow microparticle having hollow submicroparticles disposed thereon.

22. The hollow inorganic microparticle of claim 21, wherein the hollow microparticle and the hollow submicroparticles are formed as a single entity.

23. The hollow inorganic microparticle of claim 21 or 22, wherein the submicroparticles partially or entirely cover the hollow microparticle.

24. The hollow inorganic microparticle of any one of claims 21 to 23, wherein the hollow microparticle comprises a diameter ranging from 1 μηι to 100 μπι.

25. The hollow inorganic microparticle of any one of claims 21 to 24, wherein each of the hollow submicroparticles comprises a diameter ranging from 1 nm to less than 1 μηι.

26. The hollow inorganic microparticle of any one of claims 21 to 25, wherein the hollow microparticle and/or the hollow submicroparticles are monodispersed or polydispersed.

27. The hollow inorganic microparticle of any one of claims 21 to 26, wherein the hollow microparticle and/or the hollow submicroparticles are spherical or non- spherical.

28. The hollow inorganic microparticle of any one of claims 21 to 27, wherein the hollow inorganic microparticle is composed of silica, gold, silver, or palladium.

29. The hollow inorganic microparticle of any one of claims 21 to 28, wherein the hollow inorganic microparticle comprises a mesoporous shell.