Method for synthesising microparticles

Abstract

A method for synthesizing mesoporous silica microparticles comprising the steps of: preparing a sol from an ammonium catalyzed hydrolysis and condensation reaction of a pre-sol solution comprising a silica precursor and a structure directing agent dissolved in a mixed solvent system comprising an alcohol and water to produce mesoporous particles of silica with an average diameter of up to about 50 μm; hydrothermally treating the particles to increase the pore size; treating the particles to remove residual structure directing agent; and further increasing the pore size using controlled dissolution.

Claims

1. A method for synthesizing discrete, spherical mesoporous silica microparticles having a random pore structure comprising the steps of: producing mesoporous particles of silica with an average diameter of up to 50 μm by preparing a sol from an ammonium catalyzed hydrolysis and condensation reaction of a pre-sol solution comprising a silica precursor and a structure directing agent which is a surfactant dissolved in a mixed solvent system comprising water and an alcohol which is one or more of ethanol, methanol, 1-propanol, 2-propanol, and 1-butanol, wherein the mole ratio of silica precursor:structure directing agent:alcohol:water:ammonia catalyst is in the range from (0.001-0.08):(0.001-0.006):(8-14):(2-10):(0.05-1.5); hydrothermally treating the particles in an amine-water emulsion to increase the pore size; heating the particles to a temperature of 400° C. to 800° C. or treating the particles with microwave irradiation to remove residual structure directing agent; and further increasing the pore size of the particles using an etching process utilising a base catalyst which is one or more of ammonium hydroxide, sodium hydroxide, potassium hydroxide, lithium hydroxide and calcium hydroxide; wherein the silica precursor is one or more selected from the group consisting of: tetraethoxysilane (TEOS), tetramethoxysilane (TMOS), tetrapropoxysilane (TPOS), tetrabutoxysilane (TBOS), tetra-acetoxysilane and tetrachlorosilane or an organic derivative thereof; wherein the organic derivative has the formula:
R.sub.nSiX.sub.(4-n) wherein: R is an organic radical; X is a hydrolysable group selected from one or more of the group consisting of: halide, acetoxy, and alkoxy; and n is an integer from 1 to 4, or the silica precursor is a hybrid silica precursor selected from the group consisting of: dimethyldimethoxysilane, methyltriethoxysilane, methyltrimethoxysilane, ethyltrimethoxysilane, n-propyltrimethoxysilane, isobutyltriethoxysilane, isobutyltrimethoxysilane, phenyltrimethoxysilane, n-octyltriethoxysilane, iso-octyltrimethoxysilane, or a bridged hybrid silica precursor having the general formula:
R.sub.nX.sub.(3-n)Si—R′—Si—R.sub.nX.sub.(3-n) wherein: R is an organic radical; X is halide, acetoxy, or alkoxy; R′ is methyl, ethyl, propyl or butyl; and n is 1 or 2; the surfactant has the structure (CH.sub.3).sub.3N+C.sub.xH.sub.y, wherein x is an integer between 12 and 20, and y is an integer between 23 and 41.

2. The method of claim 1, wherein the porous particles are hydrothermally treated at a temperature of between 70° C. and 150° C.

3. The method of claim 1, wherein the amine to water ratio is between 1 v/v % and 10 v/v %.

4. The method of claim 1, wherein the amine is N,N-dimethyldecylamine, trioctylamine, trimethylamine, tridodecylamine, trimethylamine, or combinations thereof.

5. The method of claim 1, wherein the structure directing agent is cetyltrimethylammonium bromide (CTAB).

6. The method of claim 1, wherein in the etching process: (i) the base catalyst is present in a concentration of between 0.01 M and 1 M; (ii) the particles are etched for up to 12 hours or for between 1 day to 5 days; (iii) the particles are etched at a temperature of 50° C.; (iv) the etching process comprises a silica chelating or complexing agent; (v) the base catalyst is ammonium hydroxide; (vi) or combinations thereof.

7. The method of claim 1, wherein: (i) the particles are treated for 1 hour to 24 hours to remove residual structure directing agent; (ii) the particles are treated in the presence of an alcohol to remove residual structure directing agent; or (iii) a combination of (i) and (ii).

8. The method of claim 1, wherein the silica precursor is 1,2-Bis(triethoxysilyl)ethane.

9. The method of claim 1, wherein (i) the mole ratio of silica precursor:structure directing agent:alcohol:water:ammonia catalyst is 0.0359:0.0032:12.36:6.153:0.505; (ii) the pre-sol solution is maintained at a temperature of −5° C. to 80° C.; (iii) the pre-sol solution is agitated; (iv) a dopant compound is added to the pre-sol solution; or (v) any combination of (i)-(iv).

Description

BRIEF DESCRIPTION OF DRAWINGS

(1) The invention will be more clearly understood from the following description thereof given by way of example only with reference to the accompanying figures in which:

(2) FIG. 1 is a flow diagram illustrating a process according to the invention.

(3) FIG. 2A is a scanning electron micrograph image of porous silica spheres prepared by a method of the invention from the moles ratios TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 0.0359:0.003:12.36:0.5:6.15 shown at ×5,500 magnification.

(4) FIG. 2B is a scanning electron micrograph image of porous silica spheres prepared by a method of the invention from the moles ratios TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 0.0359:0.003:12.36:0.5:6.15 shown at ×18,000 magnification.

(5) FIG. 3 illustrates particle size measurements of the porous silica particles prepared under various agitation speeds (◯) 200 rpm: (.square-solid.) 300 rpm; and (Δ) 400 rpm.

(6) FIG. 4A is a graph showing the effect of changing experimental conditions during the synthesis process on the average particle size produced from a moles ratio of TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 00359:0.032:12.36:0.0505:6.153 as measured by SEM. The experimental condition changed was volume of TEOS. (*=polydisperse size, largest particle size taken).

(7) FIG. 4B is a graph showing the effect of changing experimental conditions during the synthesis process on the average particle size produced from a moles ratio of TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 00359:0.032:12.36:0.0505:6.153 as measured by SEM. The experimental condition changed was volume of ammonium hydroxide.

(8) FIG. 4C is a graph showing the effect of changing experimental conditions during the synthesis process on the average particle size produced from a moles ratio of TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 00359:0.032:12.36:0.0505:6.153 as measured by SEM. The experimental condition changed was volume of methanol (*=polydisperse size, largest particle size taken).

(9) FIG. 4D is a graph showing the effect of changing experimental conditions during the synthesis process on the average particle size produced from a moles ratio of TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 00359:0.032:12.36:0.0505:6.153 as measured by SEM. The experimental condition changed was mass of CTAB**=particle agglomeration, no discrete particles observed).

(10) FIG. 4E is a graph showing the effect of changing experimental conditions during the synthesis process on the average particle size produced from a moles ratio of TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 00359:0.032:12.36:0.0505:6.153 as measured by SEM. The experimental condition changed was reaction temperature.

(11) FIG. 5A is a graph showing the Barrett, Joyner, Halenda (BJH) pore size measurements of porous silica particle produced at a chemical molar ratio of TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 0.0359:0.003:12.36:0.5:6.15 untreated (.square-solid.) and treated (•) with a neutral amine (DMDA);

(12) FIG. 5B is a graph showing nitrogen adsorption (.square-solid.) and desorption (◯) isotherms of DMDA treated and untreated particles.

(13) FIG. 6A is a graph showing the BJH pore size measurement of sodium hydroxide etched particles after base etching (controlled dissolution) for 3 days;

(14) FIG. 6B is a graph showing nitrogen adsorption (.square-solid.) and desorption (◯) isotherms of sodium hydroxide etched particles after base etching (controlled dissolution) for 3 days.

(15) FIG. 7A is a graph showing the BJH pore size measurement of sodium hydroxide etched particles after base etching (controlled dissolution) for 3 days (line A) and after a double base etching (controlled dissolution) (line B);

(16) FIG. 7B is a graph showing nitrogen adsorption (↑) and desorption (↓) isotherms of sodium hydroxide etched particles after base etching (controlled dissolution) for 3 days (line A) and after a double base etching (controlled dissolution) (line B).

(17) FIG. 8A is a graph showing nitrogen absorption (↑) and desorption (↓) isotherms of ammonium hydroxide base etched particles after base etching under different experimental conditions (different concentrations of ammonium hydroxide and base etching for different lengths of time—see Table 2 for the experimental conditions);

(18) FIG. 8B is a graph showing the BJH pore size measurement of ammonium hydroxide etched particles after base etching under different experimental conditions (different concentrations of ammonium hydroxide and base etching for different lengths of time—see Table 2 for the experimental conditions).

(19) FIG. 9 is a TEM image of the particles produced by a process of the invention showing the expanded pore system; and

(20) FIG. 10 is a scanning electron micrograph image of porous silica spheres prepared by a process of the invention from the moles ratios TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 0.0359:0.003:12.36:0.5:6.15 shown at ×2,200 magnification. (Reaction temperature was −17° C.).

DETAILED DESCRIPTION

(21) We have devised a simple and reproducible method for synthesizing discrete size-monodisperse micrometer porous particles with an average size of up to about 50 μm such as up to about 5 μm or with an average size in the range of about 0.1 to about 3 μm. The method allows the preparation of uniform particles, with tunable mesoporous and macroscopic morphologies, in particular porous silica particles in the form of spheres.

(22) By careful control of the reaction conditions, such as the concentration and type of surfactants, temperature, agitation speed, hydrothermal treatment and base etching (controlled dissolution) steps, the pore size and structure of the porous spheres can be predetermined.

(23) Using the method of the invention we are able to prepare macroscopic mesoporous materials of regular, predictable and controlled shape. Previously the control of both the macroscopic and mesoporous properties of such materials has been difficult to achieve on a consistent basis.

(24) Advantageously, the method of the invention produces a high yield of mesoporous particles. For example 2.5 l of sol may yield about 20 g of mesoporous particles.

(25) The method provides mesoporous particles with a narrow size distribution. Such materials have large surface areas and are very effective for use in chromatographic, absorbent and separation applications.

(26) Porous silica particles with an average size of up to about 50 μm or up to about 5 μm or with an average size in the range of about 0.1 to about 3 μm offer a number of advantages over current commercially available porous silica spheres which include: 1) Monodispersed particle sizes 2) Tunable pore size 3) No need for hydrogen fluoride (HF) etching to increase pore size 4) No subsequent separation steps i.e. sieving 5) No Bimodal Pore size distributions 6) High yield 7) Relatively Short Preparation Time (1 week)

(27) The mesoporous materials of the invention may also be relevant to the catalysis industry as support materials and to the general materials market, including highly specific chemical sensors and opto-electronic devices.

(28) Mesopore dimensions may be tuned utilizing a water-amine emulsion hydrothermal technique and subsequent base etching techniques such as sodium hydroxide or ammonium hydroxide base etching. Spherical particles are produced in a similar manner to those reported by Shimura et al..sup.12 In the preparation, micelles formed from cationic surfactants, such as CTAB, are mixed with a silica precursor, such as tetraethoxysilane (TEOS), under basic conditions (termed a pre-sol solution) and processed to form mesoporous materials. By changing the base conditions, stirring speed and temperature relatively size-monodisperse spherical particles with tunable macroscopic diameters up to about 50 μm such as up to about 5 μm or between about 0.1 and about 3 μm can be formed. The resultant particle size can be controlled by controlling the experimental conditions of the process such as the volume of silica precursor or volume of catalyst or volume of solvent or the reaction temperature of the process. For example by controlling the amount of ammonia in the pre-sol solution, the resultant particle size can be determined. We have found that 0.0159 moles of ammonia results in particles with an average diameter of about 2.45 μm whereas 0.3971 moles of ammonia produces particles with an average diameter of about 0.49 μm. FIGS. 4A to E show the effect of increasing the volume of silica precursor (TEOS in the example of FIG. 4A): the effect of increasing the volume of catalyst (Ammonia in the example of FIG. 4B); the effect of increasing the volume of solvent (methanol in the example of FIG. 4C); the effect of increasing the mass of poreogen (CTAB in the example of FIG. 4D) and the effect of increasing temperature (FIG. 4E) on the resultant particle size. Referring to FIGS. 4A to 4E, alteration of the temperature at which the reaction takes place appears to have the most dramatic effect on particle size with a temperature of less than about 10° C. appearing to be optimum for producing larger particle sizes and a temperature of about 50° C. appearing to be optimum for producing particles with an average size of about 1 μm or less. A temperature of below about 0° C. may be utilized to produce even larger particles. For example referring to FIG. 10, a temperature of about −17° C. produces particles with an average size of about 4.7 μm and with particle sizes ranging from about 3.82 μm to about 5.52 μm.

(29) We envisage that temperatures of about −100° C. or less will produce particles with an average size of about 10 μm or more, for example up to about 50 μm.

(30) Resultant particle size may also be controlled by altering two or more experimental parameters.

(31) We envisage that large particles, such as particles with an average size of about 20 μm or more, for example up to about 50 μm could be produced using a seeded growth method. In a seeded growth method, particles obtained from the process described herein (Step 2 of FIG. 1) are immersed in a fresh sol preparation (Step 1 of FIG. 1) such that a new layer of silica is grown on the existing particles thereby increasing the average size of the particles. The average size of particles may be further increased by performing additional seeded growth steps. Once particles have been grown to the desired size they can be processed as described in steps 3 to 6 of FIG. 1. The preparation of particles using the seeded growth method may result in particles having a core-shell structure.

(32) Post synthesis treatment of the silica powder via an amine-water emulsion under hydrothermal conditions results in the controlled swelling of the mesopores to between about 2 and about 4 nm. The invention provides a method for synthesizing swelled mesoporous silica materials with tunable mesoporous diameters. Further post synthesis treatment using a base etch (controlled dissolution) solution further increases the pore size of the silica powders to between about 4 nm to about 50 nm.

(33) The method has the following advantages over mesoporous silica spheres synthesized by other procedures: i) particles can be produced which are spherical and relatively size-monodisperse allowing for efficient column packing. The particles themselves are discrete and not aggregated or linked as reported in a number of other methods. ii) the particles are thermally (up to about 850° C.), mechanically and chemically robust. iii) the mesopore diameters of the particles can be controlled between about 2 and about 50 nm. iv) the mesoporous particles act as effective stationary phases for chromatographic separations.

(34) The surfactants used may be, but are not limited to, any one or more of cationic surfactants, e.g. cetyltrimethylammonium bromide (CTAB), diblock (A-B) or triblock copolymers (A-B-A or A-B-C), with polyethylene oxide (PEO), polypropylene oxide (PPO) or polybutylene oxide (PBO) segments, polyalkyl ethers, e.g. C.sub.xH.sub.2x+1—(CH.sub.2—CH.sub.2O).sub.zH (C.sub.xEO.sub.y) such as Brij surfactants, anionic surfactants, such as sodium bis (2-ethylhexyl) sulfosuccinate (AOT) and Triton-X.

(35) The alcohol-type solvent used may be, but is not limited to, any one or more of methanol, ethanol, propanol or butanol.

(36) A suitable silica precursor may be, but is not limited to, any one or more of tetraethoxysilane (TEOS), tetramethoxysilane (TMOS), tetrapropoxysilane (TPOS), and tetrabutoxysilane (TBOS), tetra-acetoxysilane, tetrachlorosilane or organic derivative thereof represented by the formula R.sub.nSiX.sub.(4-n) where R is an organic radical and X is a hydrolysable group such as halide, acetoxy, alkoxy, teramethysilane, tetraethysilane, and n is an integer between 1 and 4.

(37) Hybrid silica precursors may also be used in the process of the invention to produce porous hybrid silica microparticles. By “hybrid silica particles” we mean silica particles that contain a percentage of organic component within the structure such as silica particles with organic functionality. The organic functionality may be within the silica particle (internal) and/or linked to the surface of the silica particle (external). A suitable hybrid silica precursor may be, but is not limited to, any one or more of, dimethyldimethoxysilane, methyltriethoxysilane, methyltrimethoxysilane, ethyltrimethoxysilane, n-propyltrimethoxysilane, isobutyltriethoxysilane, isobutyltrimethoxysilane, phenyltrimethoxysilane, n-octyltriethoxysilane, and isooctyltrimethoxysilane.

(38) Bridged hybrid precursors may also be used in the process of the invention to produce porous hybrid silica microparticles.

(39) A suitable bridged silica may be, but is not limited to
R.sub.nX.sub.(3-n)Si—R′—SiR.sub.nX.sub.(3-n) wherein: R is an organic radical; X is a hydrolysable group such as halide, acetoxy, alkoxy, teramethysilane, tetraethysilane; R′ is a bridging group and may be but not exclusive of a methyl, ethyl, propyl, butyl; and n is 1 or 2

(40) An example of a bridged hybrid silica precursor is 1,2-Bis (triethoxysilyl)ethane.

(41) A suitable amine porogenic swelling agent may be, but is not limited to, any one or more of N,N-Dimethyldecylarnine, Trioctylamine, trimethylamine, tridodecylamine and trimethylamine.

(42) The silica source used to prepare the sol may be, but is not limited to, an alkoxide, carboxylate or halide of silicon.

(43) A suitable base etch solution may be, but is not limited to, hydroxides of sodium, potassium and ammonium.

(44) A suitable silica chelating agent/complexing agent may be but is not limited to, organic diols such as catechol (1,2 benzenediol).

(45) Control of the pre-sol conditions pre-determine the macroscopic particle size of the particles. Decreased concentration of the base hydrolysis agent yields larger particles, whilst increased temperature yields smaller particles.

(46) The invention will be more clearly understood by the following examples thereof.

EXAMPLES

Example 1

(47) Mesoporous silica particles are prepared in several stages, as represented schematically in FIG. 1 and described below:

(48) Step 1: CTAB (about 0.001 to about 0.006 moles, typically about 0.0032 moles) is first dissolved in methanol (at a concentration of about 8 to about 14 moles, typically about 12.36 moles). Ammonia (about 0.05 to about 1.5 moles, typically 0.505 moles) and water (about 2 to about 10 moles, typically about 6.153 moles) are added to the mixture and stirred for 15 minutes before the one step addition of TEOS (about 0.001 to about 0.08 moles, typically about 0.00826 moles). The silica precursor is typically present at a concentration of between about 5 to about 25% v/v of the pre-sol). The sol is allowed to stir for between 24 and 96 hours. The pre-sol solution may be prepared at temperatures between −5 and 80° C. and agitation speed of between 0 and 1000 rpm. The pre-sol solution should be clear and free from any visible particles to produce high quality porous particles.

(49) When the process is used to make hybrid silica particles the TEOS may be replaced with a suitable hybrid silica precursor. Alternatively, when making bridged hybrid silica particles the silica precursors may comprise a mixture of a bridged hybrid silica precursor and a non-hybrid silica precursor for example TEOS. When using a mixture of bridged hybrid silica precursors and non-hybrid silica precursor, the non-hybrid silica precursor may be present at a concentration of between about 5 to about 25% v/v of the pre-sol solution.

(50) Step 2: The silica precipitate is separated by filtration (vacuum filtration through a Whatman 110 mm diameter filter paper) and dried at room temperature to produce an as synthesized silica powder of porous silica particles.

(51) Step 3: An emulsion of DMDA in H.sub.2O (3.3% v/v) is prepared by vigorously stirring known amounts of DMDA in water for 1 hour. As synthesized silica powder (2.5% w/w) from step 2 is added to the emulsion and stirred for a further hour. The solution is then transferred to a closed hydrothermal container and treated at about 110° C. for 1 week under autogenous pressure. A color change from white to brown is observed.

(52) Step 4: The porous silica particles are removed from the hydrothermal process of step 3, washed, filtered, air dried for up to 4 days and calcined at temperatures between about 200 and about 550° C. for periods of a few minutes to several days in air or air/ozone mixtures. Alternatively, the particles are exposed to microwave irradiation between about 40 and about 1000 watt in the presence of a solvent which in most cases is an alcohol to extract the SDA. For hybrid silica particles, microwave irradiation may be used to extract the SDA. Oxide particles are formed which consist of open pores, i.e. no organic surfactant is present.

(53) Step 5: The hydrothermally treated and calcined particles (1% w/w) are base etched. The calcined particles may be added to a 0.05 M sodium hydroxide base etch solution and agitated for about 3 days. Alternatively, the calcined particles may be base etched using an ammonium hydroxide base etch solution for example a base etch solution comprising about 14.8M ammonium hydroxide and agitated for about 8 hours. The base etch step may be performed at a temperature of about 50° C. Optionally, a silica chelating agent or complexing agent can be included in the base etching solution which may reduce the likelihood of Ostwald ripening of the etched particles. As an example Catechol may be added to the base etch solution at a concentration of about 10 v/v %. Catecol may be included in the base etching solution when the base etching catalyst is a hydroxide of sodium or ammonium.

(54) The rate of the base etching step (controlled dissolution of silica) can be controlled by controlling one or more of the reaction parameters such as time, temperature, concentration of base etching catalyst, concentration of silica chelating agent or complexing agent, and the agitation conditions.

(55) Step 6: The etched particles are separated by filtration (vacuum filtration through a Whatman 110 mm diameter filter paper) and dried at 200° C.

(56) Step 7: The porous particles can be packed into traditional chromatography columns, with typical dimensions such as diameter 1.0 cm and length 30 cm, using traditional ‘wet filling’ techniques, i.e. the mesoporous silica is wetted with a solvent to produce a slurry which is delivered into the column. A liquid sample of the mixture to be chromatographed is dissolved in a solvent, typically dichloromethane, and placed on top of the column. The starting column solvent (hexane in the first two cases) is then placed into the column. A hand pump can then be used to generate the required pressure to force the solvent through the column to separate the mixture's components.

Example 2

Preparation of Mesoporous Silica Spheres

(57) Mesoporous silica spheres were prepared based on modified methods described by Shimura et al..sup.12 and Unger et al..sup.15 Tetraethoxysilane (TEOS) was used as the silica precursor, while cetyltrimethylammonium bromide (CTAB) acted as the surfactant template. Methanol (MeOH) was used as the co-solvent.

(58) In a typical reaction, 1.25 g of CTAB was mixed in a 2 L beaker with 88 ml of H.sub.2O and 500 ml of methanol and was left stirring (200 rpm) for 10 mins. 32 ml of NH.sub.4OH was then added to the solution and the system was left stirring for a subsequent 10 mins. Finally 8 ml of TEOS was added to the solution in a one step addition and the stirring speed increased to 300 rpm. The reaction temperature was controlled at 16° C. The liquid suspension was filtered from the beaker after 24 hours and was subsequently washed with MeOH. It was air-dried at room temperature for 2 hours. A known mass of the as-synthesized material was then added to a pre-prepared agitated water-DMDA (3.3% v/v) emulsion system. After subsequent agitation for 1 hour the contents were transferred to a hydrothermal cell and placed in a 110° C. oven for 6 days. Calcination of the surfactant template was performed at 550° C. for 8 hr. The calcined product was then placed in a 0.05 M NaOH (1% w/w) solution and agitated at 200 rpm for 3 days, filtered and dried at 200° C. The Silica particles were ‘etched’ for a second time (under the same conditions: 0.05 M NaOH (1% w/w) solution and agitated at 200 rpm for 3 days) to further increase pore size, filtered and dried at 200° C. Table 1 illustrates the molar composition and physiochemical properties of a variety of silica particles synthesized.

(59) TABLE-US-00001 TABLE 1 Physiochemical properties of synthesized silica particles prepared from a mole ratio of TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 0.0359:0.0032:12.36:0:505:6.153 Sample w.sub.BJH/nm S.sub.BETm.sup.2g.sup.−1 V.sub.BJH/cm.sup.3g.sup.−1 Untreated 1.78 704 0.45 DMDA Treated 4.72 599 0.74 Base Etch Treated 7.10 to 8.1  197 to 305 0.448 to 0.777 Base Etch Treated 2 12.1 to 20.6 179 to 201 0.675 to 0.87  Note: Average pore diameter (w.sub.BJH), surface area (S.sub.BET), and pore volume (V.sub.BJH) calculated from nitrogen adsorption measurements. (1 nm is equivalent to 10 Å)

Example 3

Preparation of Mesoporous Silica Spheres

(60) Mesoporous silica spheres were prepared based on modified methods described by Shimura et al..sup.12 and Unger et al..sup.15 Tetraethoxysilane (TEOS) was used as the silica precursor, while cetyltrimethylammonium bromide (CTAB) acted as the surfactant template. Methanol (MeOH) was used as the co-solvent.

(61) In a typical reaction, 1.25 g of CTAB was mixed in a 2 L beaker with 88 ml of H.sub.2O and 500 ml of methanol and was left stirring (200 rpm) for 10 mins. 32 ml of NH.sub.4OH was then added to the solution and the system was left stirring for a subsequent 10 mins. Finally 8 ml of TEOS was added to the solution in a one step addition and the stirring speed increased to 300 rpm. The reaction temperature was controlled at 16° C. The liquid suspension was filtered from the beaker after 24 hours and was subsequently washed with MeOH. It was air-dried at room temperature for 2 hours. A known mass of the as-synthesized material was then added to a pre-prepared agitated water-DMDA (3.3% v/v) emulsion system. After subsequent agitation for 1 hour the contents were transferred to a hydrothermal cell and placed in a 110° C. oven for 6 days. Calcination of the surfactant template was performed at 550° C. for 8 hr.

(62) The calcined product was then placed in a sodium hydroxide solution under the conditions listed in Table 2 below and agitated at 200 rpm and 50° C. for the time indicated in Table 2 below. Following sodium hydroxide etching, the particles were filtered and dried at 200° C.

(63) Particles with the following properties were synthesized:

(64) TABLE-US-00002 TABLE 2 Physiochemical properties of synthesized silica particles prepared from a mole ratio of TEOS:CTAB:MeOH:NH .sub.3:H.sub.2O of 0.0359:0.0032:12.36:0:505:6.153 Etching Sample S.sub.BET/ V.sub.BJH/ w.sub.BJH/ w/v % Temp/ Time/ I.D m.sup.2g.sup.−1 cm.sup.3g.sup.−1 nm SiO.sub.2:NH.sub.4OH ° C. hrs NH3002 352 0.52 116 1 50 3 NH3004 117 0.3 157 5.7 50 6.5 NH3005 104 0.37 250 34 50 10 NH3006 200 0.38 124 34 50 8 NH3007 88.5 0.26 240 34 50 12 Note: Average pore diameter (W.sub.BJH), surface area (S.sub.BET), and pore volume (V.sub.BJH) calculated from nitrogen adsorption measurements. (1 nm is equivalent to 10 Å)

(65) Advantageously, we have found that a single base etch step using ammonium hydroxide does not cause aggregation of the monodisperse particles. Particles produced by the process of Example 3 remain monodisperse following base etching with an ammonium hydroxide base etch solution.

Example 4

Preparation of Mesoporous Silica Spheres

(66) Using the method of Example 2 but varying the concentration of ammonia resulted in particles with an increased average diameter. In this Example a mole ratio of TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 0.0359:0.0032:12.36:0.0159:6.153 was used.

(67) In a typical reaction, 1.25 g of CTAB was mixed in a 2 L beaker with 107.6 ml of H.sub.2O and 500 ml of methanol and was left stirring (200 rpm) for 10 mins. 4 ml of NH.sub.4OH was then added to the solution and the system was left stirring for a subsequent 10 mins. Finally 8 ml of TEOS was added to the solution in a one step addition and the stirring speed increased to 300 rpm. The reaction temperature was controlled at 16° C. The liquid suspension was filtered from the beaker after 24 hours and was subsequently washed with MeOH. It was air-dried at room temperature for 2 hours. A known mass of the as-synthesized material was then added to a pre-prepared agitated water-DMDA (3.3% v/v) emulsion system. After subsequent agitation for 1 hour the contents were transferred to a hydrothermal cell and placed in a 110° C. oven for 6 days. Calcination of the surfactant template was performed at 550° C. for 8 hr. Silica particles with an average diameter of 2.45 μm were obtained. The calcined product was then placed in a 0.05 M NaOH (1% w/w) solution and agitated at 200 rpm for 3 days, filtered and dried at 200° C. to increase the pore size to about 7.1 nm to 8.1 nm. Optionally, the Silica particles were ‘etched’ for a second time (under the same conditions: 0.05 M NaOH (1% w/w) solution and agitated at 200 rpm for 3 days) to further increase pore size to about 12.1 nm to 20.6 nm, filtered and dried at 200° C.

Example 5

Preparation of Mesoporous Silica Spheres

(68) Using the method of Example 4 but replacing the sodium hydroxide base etching steps with a single ammonium hydroxide base etching step under the conditions for NH3002 to NH3007 listed in Table 2 above at 50° C. with agitation at 200 rpm, the pore size of the particles was increased to about 11.6 nm (NH3002), about 15.7 nm (NH3004), about 25.0 nm (NH3005), about 12.4 nm (NH3006) and about 24.0 nm (NH3007). Following base etching, particles were filtered and dried at 200° C.

Example 6

Preparation of Mesoporous Hybrid Silica Spheres

(69) In a typical reaction, 1.25 g of CTAB was mixed in a 2 L beaker with 88 ml of H.sub.2O and 500 ml of methanol and was left stirring (200 rpm) for 10 mins. 32 ml of NH.sub.4OH was then added to the solution and the system was left stirring for a subsequent 10 mins. Finally, 7 ml of methyltrimethoxysilane was added to the solution in a one step addition and the stirring speed increased to 300 rpm. The reaction temperature was controlled at 16° C. The liquid suspension was filtered from the beaker after 24 hours and was subsequently washed with MeOH. It was air-dried at room temperature for 2 hours. A known mass of the as-synthesized material was then added to a pre-prepared agitated water-DMDA (3.3% v/v) emulsion system. After subsequent agitation for 1 hour the contents were transferred to a hydrothermal cell and placed in a 110° C. oven for 6 days. Removal of the surfactant template was performed using microwave extraction in ethanol. The hybrid silica particles were then ‘etched’ using ammonium hydroxide under the conditions outlined in Examples 3 and 5 above.

Example 7

Preparation of Mesoporous Bridged Hybrid Silica Spheres

(70) In a typical reaction, 1.25 g of CTAB was mixed in a 2 L beaker with 88 ml of H.sub.2O and 500 ml of methanol and was left stirring (200 rpm) for 10 mins. 32 ml of NH.sub.4OH was then added to the solution and the system was left stirring for a subsequent 10 mins. Finally, 8.14 ml of 1,2-Bis (triethoxysilyl)ethane was added to the solution in a one step addition and the stirring speed increased to 300 rpm. The reaction temperature was controlled at 16° C. The liquid suspension was filtered from the beaker after 24 hours and was subsequently washed with MeOH. It was air-dried at room temperature for 2 hours. A known mass of the as-synthesized material was then added to a pre-prepared agitated water-DMDA (3.3% v/v) emulsion system. After subsequent agitation for 1 hour the contents were transferred to a hydrothermal cell and placed in a 110° C. oven for 6 days. Removal of the surfactant template was performed using microwave extraction in ethanol. The bridged silica particles were then ‘etched’ using ammonium hydroxide under the conditions outlined in Examples 3, 5, and 6 above.

(71) The surface areas of the calcined mesoporous silica spheres were measured using nitrogen Brunauer Emmett Teller (BET) isotherms on a Micromeritics Gemini 2375 volumetric analyzer. Each sample was degassed for 12 hr at 200° C. prior to a BET measurement. The average pore size distribution of the calcined silicas was calculated on the Barrett Joyner Halanda (BJH) model from a 30-point BET surface area plot. Mesoporous silicas examined exhibited a Type-IV adsorption isotherm typical of mesoporous solids. Average pore diameters were calculated from the adsorption branch of the isotherm. A JEOL 2010 (0.5 nm resolution) electron microscope operating with a 100 kV accelerating voltage was used for transmission electron microscopy (TEM). Samples were dispersed in chloroform/ethanol, and a drop of the mixture was placed on a carbon-coated copper TEM grid. Scanning electron microscopy (SEM) measurements (0.05 μm resolution) were conducted on a JEOL 5510 SEM on samples placed on carbon tape and then adhered to a brass stub. Particle size distributions were measured on a Multisizer 3 Coulter Counter which is based on the electrical sensing zone (ESZ) technique.

(72) FIG. 1 is a flow diagram of the process according to the invention, illustrating a general method of forming ordered mesoporous silica particles. First, a silica pre-sol solution is made. This may be agitated in a beaker under atmospheric conditions. The particles are then hydrolyzed in an amine water emulsion as shown in block 3. The particles are then calcined to create SDA-free particles (block 4). Finally, these particles are base etched, filtered and dried. Silicas can then be functionalized with organic species such as silanes containing alkyl chains (C.sub.n, n=8-26) such as dimethyloctadecylchlorosilane (CH.sub.3(CH.sub.2).sub.17Si(CH.sub.3).sub.2C1; C.sub.18), can be packed into chromatography columns, and used as stationary phases for UHPLC (block 7). If a hybrid silica precursor is used to make a pre-sol solution, the resulting particles are already functionalized with an organic species. Therefore, depending on the final application/use of the microparticles synthesized, it may not be necessary to further functionalize hybrid silica particles.

(73) FIGS. 2A-B shows an SEM analysis of silica microspheres synthesized from the above method. The average particle size measured was 1.4 μm. The SEM image confirms that the surface of the sphere is smooth and free from major defects. The particle size of the modified SFB method may be controlled by altering the reactant type, stoichiometry and experimental conditions. It is useful to compare the processing and particle size control of the modified SFB method with the original SFB method. Stöber et al..sup.9 systematically varied reaction parameters so that silica particle diameters could be tailored from 0.05 μm to 2 μm in diameter. Bogush et al..sup.16 extended this work, focusing on the TEOS, EtOH, NH.sub.3, H.sub.2O system to establish concentration ranges in which size-monodispersity is maintained. In both studies particle size was not found to be dependent on batch size or method of mixing. The mass fraction and particle size may also be increased by a seeded growth technique.

(74) FIG. 3 shows particle size distribution profiles for silica synthesized using the above method. Modification of the agitation speed leads to varying particle sizes. (Open Triangles 400 rpm, closed squares 300 rpm, and open circles 200 rpm).

(75) FIGS. 4A to E show the effect of altering experimental conditions on the resultant particle size.

(76) A post synthesis hydrothermal treatment in water amine emulsions was applied to expand the pore size. FIG. 5B shows nitrogen adsorption (closed squares) and desorption isotherms (open circles) isotherms of hydrothermally treated (labelled DMDA treated) and untreated particles (labelled Untreated). There is a clear transition from a Type 1 microporous (<2 nm) to a Type 4 mesoporous (2-50 nm) adsorption isotherm according to IUPAC classification..sup.17 FIG. 5A depicts the pore size distribution profiles of an untreated (closed squares) and hydrothermally treated (closed circles) silica sample. As shown in Table 1 there is a threefold increase in average pore diameter, an increase in pore volume and a decrease in surface area. No noticeable change in sphere morphology was observed by scanning electron microscopy. In agreement with Sayari,.sup.14 the pore wall thickness of the expanded silica was not found to change significantly.

(77) The pore diameter may be further increased by a base etch in sodium hydroxide or ammonium hydroxide solution. FIG. 6B shows a nitrogen adsorption (closed squares) and desorption (open circles) isotherms of sodium hydroxide etched spheres. The average pore diameter is 8.5 nm taken from the Pore size distribution profile shown in FIG. 6A. Table 1 indicates that there is a four fold increase in the pore size after base etching (controlled dissolution).

(78) FIG. 7B shows a nitrogen adsorption (↑) and desorption (↓) isotherms of silica spheres that have been etched once with sodium hydroxide (line A) and have been double etched with sodium hydroxide (line B). The average pore diameter can be seen from the Pore size distribution profile shown in FIG. 7A for spheres that have been etched once (line A) and have been double etched (line B).

(79) FIG. 8A shows nitrogen adsorption (↑) and desorption (↓) isotherms of silica spheres that have been etched with an ammonium hydroxide etching solution under various conditions (see Table 2 above for the base etching conditions). The average pore diameter can be seen from the pore size distribution profile in FIG. 8(B) for spheres that have been etched with an ammonium hydroxide base etching solution under various conditions (see Table 2 above for the base etching conditions).

(80) FIG. 9 is a TEM image of the random pore structure within the spheres after base etching in 0.05 M NaOH (3 days). Pore sizes of up to 50 nm can be created after suitable base etch conditions i.e. repeated base etching procedures. Typically pore sizes in the region of about 2 to 25 nm or about 2 to 15 nm are achieved.

(81) FIG. 10 is a scanning electron micrograph image of porous silica spheres prepared from a moles ratio of TEOS:CTAB:MeOH:NH.sub.3:H.sub.2O of 0.0359:0.003:12.36:0.5:6.15 under a reaction temperature of −17° C. The spheres have an average diameter of about 4.7 μm.

(82) The invention is not limited to the embodiments described herein but may be varied in construction and detail.

REFERENCES

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