WO2016018935A1

WO2016018935A1 - Porous composite particulate material and methods for making and using the same

Info

Publication number: WO2016018935A1
Application number: PCT/US2015/042518
Authority: WO
Inventors: Andrew E. Dadson; David Scott Jensen; Janusz ZUKOWSKI; Andrew J. MILES; Brad Lee; Daniel J. P. LAW
Original assignee: Us Synthetic Corporation
Priority date: 2014-07-29
Filing date: 2015-07-28
Publication date: 2016-02-04

Abstract

In an embodiment, a porous composite particulate material includes a plurality of composite particles. Each composite particle includes an acid-base-resistant core particle at least partially surrounded by one or more layers of acid-base-resistant shell particles. The shell particles are adhered to the core particle by a polymeric layer. The shell particles and/or core particles may be made from an acid-base-resistant material that is stable in harsh chemical conditions. For example, the shell particles and/or core particles may be made from diamond, graphitic carbon, silicon carbide, boron nitride, tungsten carbide, ultra-clean diamond, combinations of the foregoing, or other acid-base-resistant materials. The porous composite particulate materials disclosed herein and related methods and devices may be used in separation technologies, including, but not limited to, chromatography, and solid phase extraction.

Description

POROUS COMPOSITE PARTICULATE MATERIAL AND METHODS FOR MAKING AND USING THE SAME

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No. 62/030,287 filed on 29 July 2014, the disclosure of which is incorporated herein, in its entirety, by this reference.

BACKGROUND

[0002] Chromatography and solid-phase extraction ("SPE") are commonly-used separation techniques employed in a variety of analytical chemistry and biochemistry environments. Chromatography and SPE are often used for separation, extraction, and analysis of various constituents, or fractions, of a sample of interest. Chromatography and SPE may also be used for the preparation, purification, concentration, and clean-up of samples.

[0003] Chromatography and SPE relate to any of a variety of techniques used to separate complex mixtures based on differential affinities of components of a sample carried by a mobile phase with which the sample flows, and a stationary phase through which the sample passes. Typically, chromatography and SPE involve the use of a stationary phase that includes an adsorbent packed into a cartridge or column. A commonly-used stationary phase includes a silica-gel-based sorbent material.

[0004] Mobile phases are often solvent-based liquids, although gas chromatography typically employs a gaseous mobile phases. Liquid mobile phases may vary significantly in their compositions depending on various characteristics of the sample being analyzed and on the various components sought to be extracted and/or analyzed in the sample. For example, liquid mobile phases may vary significantly in pH and solvent properties. Additionally, liquid mobile phases may vary in their compositions depending on the characteristics of the stationary phase that is being employed. Often, several different mobile phases are employed during a given chromatography or SPE procedure. Stationary phase materials may also exhibit poor stability characteristics, peak shape, resolution, and column efficiency in the presence of various mobile phase compositions and/or complex mixtures for which separation is desired. The poor stability characteristics, peak shape, resolution, and column efficiency of certain stationary phase materials in some mobile phases and complex mixtures, in some cases, may even preclude the possibility of using chromatography or SPE to perform the desired separation. SUMMARY

[0005] Embodiments of the invention relate to ultra-clean diamond-containing porous composite particulate materials and apparatuses and methods using the same. In an embodiment, a method for manufacturing a porous composite particulate material is disclosed. The method includes providing a plurality of acid-base-resistant core particles and a plurality of acid-base-resistant shell particles. At least a portion of the plurality of acid-base resistant shell particles including diamond particles exhibiting a total metallic impurity content of about 60 ppm or less, such as about 40 ppm or less. The method further includes coating at least a portion of the plurality of acid-base-resistant core particles, at least a portion of the plurality of acid-base-resistant shell particles, or combinations thereof with polymer material and adhering them together to form a plurality of composite particles.

[0006] In an embodiment, a porous composite particulate material is disclosed. The porous composite material includes a plurality of composite particles, with each composite particle including an acid-base-resistant core particle and a plurality of acid- base-resistant shell particles. At least portion of the plurality of acid-base-resistant shell particles includes diamond particles exhibiting a total metallic impurity content of about 60 ppm or less, such as about 40 ppm or less. The porous composite material further includes a polymeric layer bonding the plurality of shell particles to the acid-base- resistant core particle.

[0007] In an embodiment, a method of using a porous composite particulate material is disclosed. The method includes placing a porous composite particulate material in a vessel. The porous composite particulate material includes a plurality of composite particles. Each composite particle includes an acid-base-resistant core particle, a plurality of acid-base-resistant shell particles, and a polymeric layer bonding of the plurality of shell particles to the core particle. At least portion of the plurality of acid-base-resistant shell particles includes diamond particles exhibiting a total metallic impurity content of about 60 ppm or less. The method additionally includes providing a mobile phase including at least two different components to be separated and flowing the mobile phase through the porous composite particulate material to physically separate the at least two different components. The method further includes recovering at least one of the two different components that have been separated.

[0008] Features from any of the disclosed embodiments may be used in combination with one another, without limitation. In addition, other features and advantages of the present disclosure will become apparent to those of ordinary skill in the art through consideration of the following detailed description and the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The drawings illustrate several embodiments of the invention, wherein identical reference numerals refer to identical or similar elements or features in different views or embodiments shown in the drawings.

[0010] FIG. 1 is a schematic flow diagram illustrating a method for making a composite particulate material according to an embodiment;

[0011] FIG. 2 is a schematic flow diagram illustrating another method for making a composite particulate material according to an embodiment;

[0012] FIG. 3 is a cross-sectional view of a vessel used for forming a body of bonded composite particles according to an embodiment;

[0013] FIG. 4 is a cross-sectional view of a composite particle according to an embodiment;

[0014] FIG. 5 is a cross-sectional view of an embodiment of a separation apparatus including a porous body comprising any of the porous composite particulate materials disclosed herein;

[0015] FIG. 6 is a scanning electron microscope ("SEM") image of composite particles according to an embodiment;

[0016] FIG. 7 is a side-by-side comparison of the respective pore volumes versus pore diameters of 3 μιη silica and a composite particle having 15 nm ultra-clean diamond shell particles in a 133 nm thick shell according to an embodiment;

[0017] FIG. 8A is a side-by-side comparison of chromatograms showing the results of the separation of parabens in HPLC columns having core-shell particles including conventionally cleaned diamond shell particles in a masked state and an unmasked state respectively;

[0018] FIGS. 8B-8D are chromatograms and portions of chromatograms showing the results of the separation of parabens in HPLC columns having core shell particles including ultra-clean diamond shell particles in a masked state and an unmasked state respectively, according to embodiments; and

[0019] FIGS. 9A and 9B are HPLC chromatograms showing the results of the separation of analytes using HPLC columns including core shell particles having ultra- clean diamond shell particles according to an embodiment. DETAILED DESCRIPTION

[0020] Embodiments of the invention relate to ultra-clean diamond-containing porous composite materials and apparatuses and methods using the same.

I. Components Used To Make Porous Composite Particulate Materials

A. Acid-Base-Resistant Particles

[0021] The porous composite particulate materials disclosed herein include a plurality of composite particles. Each composite particle includes an acid-base-resistant core particle, and a plurality of acid-base-resistant shell particles that at least partially surround and are bonded to the core particle by a polymeric layer of polymer material to impart a desired size, surface area, and/or porosity (e.g., pore volume). The core particles and shell particles may be made from the same material or different materials. The core particles and/or shell particles may be a solid, porous, composite, synthetic, and/or natural occurring material, at least a portion of the shell particles being ultra-clean diamond, such as ultra-clean nano-scale diamond.

[0022] The core particles and the shell particles may have the same or different particle sizes. As used herein, the phrase "particle size" means the approximate average particle size, such as average diameter or other average cross-sectional dimension of a plurality of particles, unless otherwise specified. In an embodiment, the shell particles are much smaller than the core particles to achieve a desired composite-particle surface area. In an embodiment, the shell particles have a particle size that is in a range from about 1 nm to 1000 nm, more specifically in a range from about 2 nm to about 500 nm, even more specifically in a range from about 5 nm to about 200 nm, and yet even more specifically in a range from about 10 nm to about 100 nm (e.g., about 10 nm to about 20 nm). In some embodiments, the core particles may have a particle size in a range from about 0.1 μιη to about 500 μιη, more specifically about 1 μιη to about 200 μιη, or even more specifically in a range from about 0.5 μιη to about 100 μιη. The desired particle size of the core particles may depend on the application in which the composite particle is to be used. In one embodiment, the core particles have a particle size in a range from about 1 μιη to 10 μιη, more specifically about 1.5 μιη to about 7 μιη. This range may be suitable for high performance liquid chromatography ("HPLC") applications and the like. In another embodiment, the particle size of the core particles may be in a range from about 5 μιη to about 500 μιη, or more specifically in a range from about 10 μιη to about 150 μιη. This larger range may be suitable for solid phase extraction applications and the like. [0023] The acid-base-resistant shell and/or core particles may have a composition that is selected to be stable in sundry mobile phases, including organic solvents, and chemically harsh acids and bases. Examples of acid-base-resistant materials from which the shell particles and/or the core particles may be made include, but are not limited to, diamond, graphitic carbon (e.g., graphite), silicon carbide, carbonized polymer(s) (such as any polymer described herein), or another suitable material that is chemically stable in acids and bases over a selected pH range, such as a pH range of at least about 1 to about 13, such as about 3 to about 12. For example, diamond, graphite, and silicon carbide are chemically stable in acids and bases over a pH range of about 0 to about 14, with diamond materials being particularly stable at the extremes of the pH range. Examples of acid-base-resistant diamond materials from which at least some of the shell particles may be made include, but are not limited to, natural diamond particles and synthetic diamond particles, such as ultra-dispersed diamond ("UDD") particles. For example, UDD particles typically include a polycrystalline diamond core at least partially surrounded by a metastable sp² hybridized carbon shell. Such ultra-dispersed diamond particles may exhibit a particle size of about 1 nm to about 100 nm and more typically, about 2 nm to about 20 nm, and agglomerates of ultra-dispersed diamond particles may be between about 2 nm to about 200 nm. For example, the metastable sp² hybridized carbon shell may include amorphous carbon, carbon onion (i.e., closed shell sp² nanocarbons), graphitic carbon, or combinations of the foregoing. Silica and alumina are examples of materials that are not acid-base-resistant materials, because they may significantly degrade in bases with a pH greater than 8. Other relatively acid-base-resistant materials include, but are not limited to, boron nitride and tungsten carbide.

[0024] Diamond possesses remarkable chemical inertness, hardness, low compressibility, optical transparency, and high thermal conductivity that may help eliminate or reduce thermal gradients in ultra performance liquid chromatography. Unlike silica, diamond does not easily dissolve in aqueous alkaline or acidic media, and it may be used in extremely harsh chemical environments. These properties of diamond may be achieved with naturally occurring diamond and/or synthetic diamond. Diamond material may also include other inorganic carbon materials, such as graphitic carbon, fullerenes, combinations thereof, or other non-diamond carbon. When used in chromatography columns, diamond material having other inorganic carbon material and/or metallic impurities (e.g., on the surface thereof) has been demonstrated to cause tailing in the resulting chemical separations. As explained in more detail below, diamond particles may be leached such that they exhibit less than about 60 parts per million ("ppm") of total metallic impurities ("ultra-clean diamond particles"), such as about 50 ppm or less, about 40 ppm or less, about 30 ppm or less, about 21 ppm or less, or about 10 ppm or less of total metallic impurities.

[0025] The acid-base-resistant shell and core particles may be produced through any suitable method, including, for example, by forming carbonaceous material into diamond material under ultra-high pressure and high-temperature conditions or other synthetic diamond particles. Acid-base-resistance core and/or shell diamond particles, such as UDD particles, may be formed via detonation synthesis, or laser synthesis, normally resulting in nanoscale diamond particles. Additionally, the acid-base-resistant shell and core particles may be the product of natural processes or by chemical vapor deposition processes. Acid-base-resistant shell and core particles may be produced by crushing and/or grinding starting material to obtain a desired sized particle. In an embodiment, the acid-base-resistant core particles may comprise submicron to micron-sized diamond particles with, for example, a particle size of about 0.1 μιη to about 500 μιη (e.g., about 1 μιη to about 100 μιη) and the acid-base-resistant shell particles may comprise diamond particles, with for example, a particle size of about 1 nm to 1000 nm (e.g., about 2 nm to about 200 nm). The acid-base-resistant shell and/or core particles may have a spherical shape, a faceted shape, an irregular shape, or other suitable geometry.

[0026] Diamond particles, particularly UDD particles, typically include metallic impurities, and may include secondary interaction sites on the surface thereof (e.g., secondary reaction or adsorption sites). Metallic impurities common in diamond particles include, but are not limited to, transition metals, metalloids, alkaline metals, and alkaline earth metals. Specifically, such metallic impurities may include, but are not limited to, aluminum, boron, cobalt, chromium, iron, magnesium, manganese, sodium, niobium, sodium, nickel, lead, silicon, tin, titanium, tungsten, and combinations of the foregoing. The secondary interaction sites may include sp² hybridized carbon-containing materials (e.g. , graphitic carbon, fullerenes, combinations thereof, or other non-diamond carbon) on the surface of the UDD particle. The metallic impurities and/or secondary interaction sites may cause unintended interactions at the surface of the diamond particles including unintended reactivity and/or secondary adsorption sites. Undesirable or unintended secondary interactions may decrease or otherwise deteriorate peak shape, resolution, and column efficiency in chromatography separations. [0027] Unleached diamond particles may include one or more metallic impurities (e.g., thereon, therein, mixed therewith, or combinations thereof). The amount of each metallic impurity present in the unleached diamond particles may be less than about 0.5 ppm to over 100 ppm, such as more than about 250 ppm. The sum of all metallic impurities present in the unleached diamond particles may be about 90 ppm or more. Typically, individual diamond particles that are treated or cleaned using a leaching process. After the leaching process, the amount of each metallic impurity present in the cleaned diamond particles (e.g., individual cleaned diamond particles) may be less than about 0.5 ppm to over 10 ppm each. The sum of all metallic impurities present in the diamond particles cleaned in the leaching process may be about 50 ppm or higher, such as about 80 ppm or more.

[0028] As described in more detail below, the majority of metallic impurities in the diamond particles may be removed through a leaching process which includes immersing the diamond particles in a leaching solution (e.g., an acid or base) selected to dissolve the metallic impurities without dissolving the diamond particles. Such leaching processes may result in diamond particles having substantially reduced amounts of metallic impurities and/or secondary interaction sites compared to conventional leaching processes. Ultra-clean diamond particles may be particularly suitable for use as core and/or shell particles due to reduced metallic impurities and secondary interaction sites (e.g., on the surface thereof).

[0029] Ultra-clean diamond particles suitable for use as shell and/or core particles as described herein may exhibit (e.g., on a surface or volumetrically) metallic impurities (e.g., the sum of metallic impurities) in an amount of about 40 ppm or less, such as less than about 1 ppm to about 40 ppm, about 3 ppm to about 30 ppm, about 5 ppm to about 21 ppm, about 1 ppm to about 10 ppm, about 2 ppm to about 15 ppm, about 30 ppm or less, about 25 ppm or less, about 21 ppm or less, about 10 ppm or less, or about 8 ppm or less. The amount of each metallic impurity present in the ultra-clean diamond particles may be less than about 0.5 ppm to about 10 ppm, such as about less than 0.1 ppm to about 6 ppm, or less than about 1 ppm to about 4 ppm. Secondary interaction sites on diamond particles, such as those present in UDD particles, may be caused by metallic impurities, sp² hybridized carbon, or other moieties present at the surface of the diamond particle. Typically, in UDD particles, sp² hybridized carbon such as graphitic carbon or amorphous carbon forms on the surface of the diamond particle during the detonation process. When used in chemical separation, the sp² hybridized carbon containing diamond surfaces may undergo unintended secondary interactions with analytes, resulting in poor column efficiency and/or poor peak shape and resolution (e.g., increased tailing). After leaching, the sp² hybridized carbon shell of the UDD particles may also be partially or substantially completely removed from the UDD particles, thereby leaving diamond particles consisting essentially of diamond (e.g., polycrystalline diamond) with the total metallic impurity content discussed above.

[0030] While generally spherical particles may be used as shell particles, generally spherical particles may also be used as core particles. The use of non-spherical core particles typically affects the back pressure and mobile phase flow profile created by the composite particles compared to non-spherical shell particles and the reproducibility of the porous composite particulate materials. Moreover, as the core particles may be substantially isolated from the mobile phase by the shell particles and polymeric materials, the materials used to make the core particles may be less compatible with the constituents of the mobile phase as compared to the shell particles. Thus, the core particles may more readily be configured to have a generally spherical geometry. In an embodiment, a generally spherical core particle includes a material selected from the group of zirconia, titania, noble metals, acid-base-resistant highly cross-linked polymers, acid-base-resistant at least partially cross-linked polymers, alumina, thorium, carbonized polymers (e.g., divinylbenzene ("DVB")), or any combination thereof.

[0031] In an embodiment, the core particle may be a composite particle of an inner particle and a cladding layer surrounding and/or partially or completely encapsulating the inner particle. The inner particle may include materials that are acid- base unstable and/or incompatible with constituents of a mobile phase. The inner particle of the core particle may include a ceramic, polymeric, or metallic material that may be unstable in acids and bases of a certain pH (e.g. silica gel in a strong acid or base) and/or incompatible with certain constituents of chromatography mobile phases. In this embodiment, the cladding layer may be made from an acid-base resistant material that gives the core particles acid-base resistant properties and/or compatibility. In an embodiment, the cladding material may be made from any of the acid-base resistant materials disclosed herein, including, but not limited to, diamond, graphitic carbon, tungsten carbide, niobium carbide, boron nitride, zirconia, noble metals, acid-base-stable highly cross-linked polymers, titania, alumina, thorium, and any combinations thereof. In contrast, the materials used in the inner particle may be made from any material upon which the cladding layer may be deposited. While not required, the materials used in the inner particle may even be acid-base unstable (e.g., susceptible to dissolution in acidic or basic solutions of a certain pH) so long as the cladding layer substantially encapsulates the acid-base unstable material.

[0032] Core particles including an inner particle and a cladding layer may be manufactured by starting with an inner particle made from ceramic, polymeric, or metal upon which the cladding layer is deposited. The inner particle may have an average diameter ranging from about 0.5 μιη to about 50 μιη, more specifically about 0.75 μιη to about 10 μιη, or even more specifically about 1 μιη to about 5 μιη. The cladding layer may be applied as a thin coating. In one embodiment, the cladding layer has a thickness less than 5 μιη, more specifically less than 1 μιη, even more specifically less than 0.5 μιη. The cladding layer may be applied to the inner particle using any technique known in the art, including but not limited to chemical vapor deposition, physical vapor deposition, atomic layer deposition, or another suitable deposition technique.

[0033] In another embodiment, the cladding layer may be formed on the inner particle by dipping the inner particles in a carbonizable polymer and then heating the material to form graphitic carbon. Those skilled in the art are familiar with reagents (e.g., resins, polymers, and catalysts) used to make graphitic carbon through pyrolysis and similar methods. To illustrate an example formula, a core particle including the cladding may be made by (i) providing a generally spherical inner particle made from a ceramic, polymer, or metal, (ii) dipping the inner particle in a melt of polymerizable resin such phenol and hexamine (6: 1 w/w); (iii) remove excess melt, (iv) heating the coated particles gradually (e.g., to 150 °C) to form the phenol formaldehyde resin around the particles; and (v) carbonizing the resin around the particles by slow heating (e.g., less than 5° C/min) to at least about 800 °C in an oxygen free oven to form a substantially impervious carbonaceous/glassy carbon shell. For example, the resin may be carbonized by heating to about 900 °C.

[0034] In yet another embodiment, the particles may be coated with the polymer by applying a polymeric material while forcing air or other gas up through the particles (e.g., fluidized bed coating processes). Producing a core particle using an inner particle and a cladding layer may be useful for forming generally spherical particles. In one embodiment, the inner particle of the core particle may be manufactured to be spherical and the cladding layer may be applied to the generally spherical inner region to yield a generally spherical core particle.

B. Polymeric Materials [0035] The coating or binding polymer used to bond to the shell particles to the core particle and/or other shell particles may be any polymeric material that may be applied as a coating to adhere the acid-base-resistant particles to one another. For example, the polymer coating may include a polymeric material comprising one or more polymers that provide the porous composite particulate material desired properties for separating components of a mobile phase. The polymer coating may include macromonomers, oligomers, and/or various polymers, without limitation. The polymer coating may include combinations and/or mixtures of different polymeric materials and/or used to form different layers of polymers as described more fully below.

[0036] In one embodiment, the polymer coating or binding polymer may include at least one amine group. The amine polymer may be selected to be chemically stable in many of the same mobile phases that diamond particles or other acid-base-resistant materials disclosed herein are stable. In an embodiment, the amine polymer includes at least one pendant amine group and/or at least one primary, secondary, tertiary, and/or quaternary amine group. In various embodiments, the polymer coating may include for example, polyallylamine, polyethylenimine, polylysine, polyvinylamine, chitosan, trimethylchitosan (i.e., quaternized chitosan), polydiallydimethyl ammonium chloride ("PDADMAC"), poly(N,N'-dimethylaminoethylmethacrylate), poly(2-vinylpyridine), poly(4-vinylpyridine), polyvinylimidazole, poly(2-(dimethylamino)ethyl acrylate), poly(2-aminoethyl methacrylate) hydrochloride, combinations of the foregoing, and/or derivatives of the foregoing.

[0037] Polyethylenimine may be present in the polymer coating in a wide range of molecular weights and degrees of branching. Chitosan may be produced by the deacetylation of chitin, and chitin may be deacetylated to various degrees. Polymers in the coating may be substantially linear or at least partially branched. Polymers including amines therein may be protonated, deprotonated, or partially protonated prior to, during, and/or following deposition on a surface. Additionally, the polymer coating may comprise any suitable naturally occurring proteins and/or peptides.

[0038] In additional embodiments, the polymer coating may include a homopolymer and/or a copolymer compound formed from monomer subunits including, for example, allylamine, vinylamine, ethylenimine, vinyl amine, lysine, arginine, histidine, 2- isocyanatoethyl methacrylate, aziridine, 1 -vinylimidazole, 1 -vinyl-2-pyrrolidone, 2- vinylpyridine, 4-vinylpyridine, 2-(dimethylamino)ethyl acrylate, 2-aminoethyl methacrylate hydrochloride, and/or 2-(tert-butyl amino )ethyl methacrylate. [0039] Additionally, the polymer coating may include any suitable monomers that may be converted into amines after polymerization by deprotection, hydrolysis, and/or by simple chemical transformation. In various embodiments, the polymer coating may include monomers based on oxazoline, which may be polymerized to form polyoxazolines and/or which may then be hydro lyzed. Amine-comprising monomers forming a polymeric compound in coating may be protonated, deprotonated, or partially protonated prior to, during, and/or following polymerization.

[0040] In at least one embodiment, monomers forming a polymer in the polymer coating may be interspersed with other monomer units such as 2-hydroxyethylacrylate, styrene, 1,3 -butadiene, methyl methacrylate, methyl acrylate, butyl acrylate, dodecyl methacrylate, acrylonitrile, acrylic acid, methacrylic acid, 4-vinylbenzyl chloride, 4- (trifluoromethyl)styrene, 3-nitrostyrene, vinyl ether, or vinyl acetate.

[0041] The polymer coating may include a polymeric compound having various chain lengths and various degrees of branching. For example, the polymeric coating may include a polymeric compound having a weight-average molecular weight or number- average molecular weight ranging from about 1,000 to about 2,500,000. In certain embodiments, the polymer coating may include a polymeric compound having a weight- average molecular weight or number-average molecular weight ranging from about 5,000 to about 100,000. Additionally, the polymer coating may include a polymeric compound having a weight-average molecular weight or number-average molecular weight ranging from about 5,000 to about 30,000 monomer units (e.g., about 15,000 monomer units to about 20,000 monomer units, or about 17,000 monomer units), or about 30,000 to about 60,000 monomer units. In additional embodiments, the polymer coating may include polymeric compounds having a weight-average molecular weight or number-average molecular weight of less than about 1 ,000. The polymer coating may optionally include oligomers having a chain length of from 2 to 100 monomer units in length. As used herein, the term "polymeric compound" includes oligomers as well as polymers of varying chain lengths and molecular weights, unless otherwise specified.

[0042] Additional information about suitable polymers for use in the porous composite particulate materials disclosed herein may also be found in United States Patent Application No. 12/039,382 filed on 28 February 2008, entitled "Methods For Direct Attachment Of Polymers To Diamond Surfaces And Articles Formed Thereby," naming Matthew R. Linford and Li Yang as inventors, which is hereby incorporated herein, in its entirety, by this reference. [0043] In some embodiments, the polymer coating includes one or more anionic polymers. Anionic polymers may be useful for ion exchange chromatography. Example of suitable anionic polymers include, but are not limited to poly(styrenesulfonic acid, sodium salt), poly(acrylic acid), poly(methacrylic acid), derivatives of these, and/or combinations of these. While the polymer coating may be suitable for separating components of a mobile phase, uncoated, exposed surfaces of the core particles and/or shell particles (e.g., diamond core and shell particles) may be functionalized for separating components of a mobile phase as an alternative to or in addition to using the polymer coating.

II. Methods For Making Porous Composite Particulate Materials

[0044] Reference is now made to FIG. 1 which illustrates a schematic flow diagram 100 of an embodiment of a method for making a porous composite particulate material from core particles, shell particles, and polymer material. FIG. 1 is a schematic illustration and does not necessarily represent the actual shape or sizes of the acid-base- resistant core particles and/or acid-base-resistant shell particles. Moreover, FIG. 1 illustrates a method for forming a single composite particle, and the porous composite particulate materials disclosed herein include a plurality of such composite particles.

[0045] In act 1 10, a plurality of acid-base-resistant core particles 114 such as any described herein, are immersed in a polymeric material that coats and at least partially surrounds each core particle 114 with a respective polymer coating 1 12. In act 120, a first portion of acid-base-resistant shell particles are adhered to each core particle 1 14 to form a first porous shell layer 116 of shell particles. The shell particles may include any shell particle material described herein (e.g., nanoscale ultra-clean diamond particles), such as UDD particles that are substantially free of total metallic impurities, less than about 40 ppm of total metallic impurities, substantially free of sp² hybridized carbon or other moieties, or combinations thereof. The shell particles adhere to the core particles 1 14 via the polymer coating 1 12. The thickness and composition of the polymer coating 112 may be any thickness that is sufficient to adhere the shell particles to the core particles 114. The thickness of the polymer coating 112 is typically sufficiently sized so that the polymer does not fill all the voids between adjacent shell particles of the first porous shell layer 116. Maintaining a relatively thin coating may help to provide a desired surface area and/or pore volume on the resulting composite particle and/or porous composite particulate material made using the same. In one embodiment, the thickness of the polymer coating 112 may be in a range from about 1 nm to about 1 μιη thick, and more specifically in a range from about 5 nm to about 100 nm or about 1 nm to about 50 nm. In an embodiment, the thickness of the polymer coating is less than the average diameter of the shell particles, more specifically the thickness is less than about half the diameter of the shell particles, and even more specifically less than one-fourth the diameter of the shell particles. The polymer coating 1 12 may be cured or otherwise chemically modified in act 120 or in subsequent acts, as described more fully below.

[0046] The portion of shell particles may be applied to each core particle 114 by suspending the shell particles in a solvent and immersing the coated core particles 114 in the suspension of shell particles or, alternatively, the suspension of shell particles may be caused to flow over the core particles 114. Any solvent suitable for suspending the core particles and/or the shell particles may be used. In one embodiment, the core particles and/or the shell particles may be suspended in water. The coating of shell particles on the coated core particles 1 14 yields intermediate composite particles 128 having rough surfaces. The rough surface includes voids (i.e., recesses in the surface) between the individual shell particles of the first porous shell layer 1 16.

[0047] A plurality of the intermediate composite particles 128 may be used as a final product if desired and/or cross-linked to improve mechanical stability. However, substantially increased surface area and/or pore volume may be achieved by repeating acts 1 10 and 120 to yield intermediate composite particles with increasing numbers of porous shell layers. As shown in act 130, a polymer coating 1 13 may be applied to the surface of the intermediate composite particle 128 to coat the shell particles of the first porous shell layer 1 16. The polymer coating 1 13 may be made from the same or a different polymeric material than the polymeric coating 1 12 used in act 1 10. The thickness of the polymer coating 113 is typically sufficiently sized so that the polymer does not fill all the voids between adjacent shell particles of the first porous shell layer 1 16. In act 140, a second portion of the shell particles may be applied to intermediate composite particle 138 to yield second intermediate composite particles 142 each having a second porous shell layer 144 of shell particles bonded to the first porous shell layer 1 16.

[0048] In act 150, yet a third polymer coating 115 may be coated on intermediate composite particle 144 to yield intermediate particles 152, with the shell particles of the second porous shell layer 144 being coated. The polymer coating 1 15 may be made from the same or a different polymeric material than the polymeric coatings 1 12 or 1 13 used in acts 1 10 or 130. The thickness of the polymer coating 1 15 is typically sufficiently sized so that the polymer does not fill all the voids between adjacent shell particles of the second porous shell layer 144, thereby creating pores in the resulting composite particle. In act 160, a third portion of shell particles may be adhered to the second porous shell layer 144 of intermediate particles 152 to yield intermediate composite particles 164 having a third porous shell layer 162 of shell particles.

[0049] The porous shell layers 1 16, 144, and 162 may have differently or similarly sized shell particles. Also, the shell particles in different layers or the same layer may have a different composition (e diamond particles, polymers, or silica particles). Shell particles in different layers or the same layer may have different or similar material compositions with different or similar properties (e diamond with metallic impurities and ultra-clean diamond). Shell particles in different layers or the same layer may be bonded using different compositions of polymer. The different shell particles, core particles, and polymers may be selected from any combination of the components described herein or components known in the art that are similar and/or provide similar function.

[0050] The act of adding additional porous shell layers may be continued until a desired number of porous shell layers, a desired shell thickness, and/or a desired surface area or pore volume is achieved for the composite particles. In one embodiment, the act of forming porous shell layers may be repeated at least 5 times, more specifically at least about 10 times, or even more specifically at least 20 times to yield composite particles having 5, 10, or 20 porous shell layers, respectively. This act continues until the desired number of porous shell layers is achieved. In one embodiment, the number of porous shell layers is at least about 3, more specifically at least about 5, even more specifically at least about 10, yet even more specifically at least 20, and most specifically at least 50. In an embodiment, the act of forming porous shell layers may be repeated until the composite particle exhibits a desired shell thickness, such as about 20 nm to about 2μ (e about 40 nm to about Ιμιη, about 50 nm to about 200 nm, about 100 nm to about 500 nm, or about 70 nm to about 135 nm).

[0051] In an embodiment, the act of forming porous shell layers may be repeated until the composite particle exhibits a desired surface area and/or porosity (e pore volume). For example, the number and thickness of porous shell layers may selected such that the resulting composite particle exhibits a surface area of about 10 m²/g or more, such as about 10 m /g to about 100 m /g, about 15 m /g to about 75 m /g, about 20 m /g to about 50 m²/g, about 25 m²/g, or over 100 m²/g. Techniques for measuring surface area of porous particles are known the art, for example, as discussed hereinbelow. In some embodiments, the act of forming porous shell layers may be repeated until the composite particles are a sufficient size to result in a porous composite particulate material exhibiting a 5 nm average pore size or greater, such as about 5 nm to about 2 μιη, about 10 nm to about 500 nm, about 20 nm to about 250 nm, about 50 nm to about 100 nm, about 100 nm to about 200 nm, or about 150 nm average pore size. In some embodiments, the act of forming porous shell layers may be repeated until the composite particles exhibit any combination of one or more of the properties described above.

[0052] The shell particles, core particles, and/or composite particles may each be completely or partially coated with the polymer coating. In many cases, the polymer coating is applied using immersion, which tends to apply a relatively even coating around an entire particle. However, in some embodiments, one or more of the acid-base-resistant particles may only be partially coated with a sufficient polymer coating to adhere to other particles. In addition, the application of the shell particles may be asymmetric so as to create asymmetric composite particles.

[0053] In some embodiments, the shape of the core particle may be substantially uniform (e.g., spherical or rectangular) such that application of one or more uniform layers of shell particles (e.g., either uniform or non-uniform individual shell particles) results in a composite particle exhibiting a substantially similar uniform shape. Substantially uniform composite particles may enable more consistent surface areas, pore sizes, and pore volumes in porous composite particulate materials made using the same.

[0054] Once the polymer has been attached to the surface of the core particles, there are numerous chemical reactions that may be performed, including cross-linking and curing. The cross-linking and/or curing may be carried out separately at any of the acts described in method 100. In one embodiment, curing may be performed for each act that results in the formation of a porous shell layer. In one embodiment, cross-linking is carried out as a final act 170. However, the act 170 is optional and embodiments also include the use of polymers that do not require curing and/or cross-linking.

[0055] In embodiments where curing and/or cross-linking is performed, the polymer coating may be cured and/or cross linked using any suitable technique such as thermal curing and/or radiation curing (e.g., curing using infrared or ultraviolet curing lights). Curing may increase the physical and/or chemical stability of the polymer coating. For example, curing may increase the stability of the polymer coating when exposed to harsh conditions, such as high and/or low pH solutions, which may allow a stationary phase including the porous composite particulate material to be cleaned and/or otherwise used under harsh conditions. Some porous composite particulate materials described herein may be used in combination with strong solvents, high pH conditions, and/or low pH conditions. The ability to clean a column under harsh conditions may enable reuse of a previously contaminated stationary phase. In at least one embodiment, curing may cause amide linkage to form between various compounds in the polymer coating. Additionally, curing may cause amide or other linkages to form between various compounds in the polymer coating and the surface of the acid-base-resistant particles.

[0056] In additional embodiments, a polymer in the coating may be allowed to react with another compound in the coating before, during, and/or after depositing the coating on the acid-base-resistant particles to increase the molecular weight of the coating. Increasing the molecular weight of the polymer may be advantageous in that the higher molecular weight coating may have increased stability in a variety of conditions.

[0057] In additional embodiments, the coating and/or at least a polymeric compound forming the coating may be cross-linked during a curing process, such as a thermal and/or pressure-induced curing process, as described above. Additionally, the curing of the coating and/or at least a polymeric compound forming the coating, may be cross linked by exposing the coating to radiation. Cross-linking may cause stable bonds to form with amine groups and/or other chemical moieties in a polymeric compound in the coating, thereby increasing the stability of coating. Additionally, cross-linking compounds in the coating using compounds having epoxy groups may produce hydroxyl groups in and/or on the coating, resulting in a change in chemical characteristics of the coating and providing potential reactive sites on the coating.

[0058] In certain embodiments, a cross-linking agent having at least two functional bonding sites may be used to effect cross-linking of at least a portion of the coating and/or at least a polymeric compound forming the coating. For example, a cross-linking agent may comprise a diepoxide compound having at least two epoxide groups, each of which may bond with an amine group. A cross-linking agent having at least two functional bonding sites may bond with at least one amine group on at least two or more polymeric molecules and/or compounds. In an additional embodiment, a cross-linking agent having at least two functional bonding sites may bond with at least one amine group on at least two separate sites on a single polymeric molecule. Additionally, a cross-linking agent having at least two functional bonding sites may bind to a polymeric compound forming the coating at only one of the at least two functional binding sites. [0059] Examples of cross-linking agents suitable for cross-linking the polymer coating and/or at least a polymeric compound forming the polymer coating may include any type of compound containing two or more amine reactive functional groups, including, for example, diisocyanates, diisothiocyanates, dihalides, diglycidyl ethers, diepoxides, dianhydrides, dialdehydes, diacrylates, dimethacrylates, dimethylesters, di- and/or triacrylates, di- and/or trimethacrylates, and/or other diesters. In at least one embodiment, acrylates and/or methacrylates may react with an amine by Michael addition.

[0060] In addition, suitable cross-linking agents may include, without limitation, 1,2,5,6-diepoxycyclooctane, phenylenediisothiocyanate, 1,4-diisocyanatobutane, 1,3- phenylene diisocyanate, 1,6-diisocyanatohexane, isophorone diisocyanate, di ethylene glycol diglycidyl ether, 1,4-butanediol diglycidyl ether, bisphenol A diglycidyl ether, poly(ethylene glycol) diglycidyl ether, poly(propylene glycol) diglycidyl ether, octanedioic acid dichloride (suberic acid dichloride), phthaloyl dichloride, pyromellitic dianhydride, 1,3-butadiene diepoxide, p-phenylene diisothiocyanate, 1,4-dibromobutane, 1,6-diiodohexane, glutaraldehyde, 1,3-butanediol diacrylate, pentaerythritol triacrylate, pentaerythritol tetraacrylate, dipentaerythritol pentaacrylate, 1,6-hexanediol dimethacrylate, and/or propoxylated (3) glyceryl triacrylate. Cross-linking agents may additionally comprise at least one functional group suitable for bonding with non-amine functional groups that may be present on polymers in the coating disclosed herein.

[0061] In at least one embodiment, an epoxide compound such as, 1,2,5,6- diepoxycyclooctane, may have at least one highly strained epoxide ring that may be reactive with various amine groups in the polymer coating. Various alcohols may be used as effective solvents for amine-epoxide reactions. Reaction of the at least one highly strained epoxide ring with an amine group in the coating may result in immobilization of hydrophobic cyclooctyl rings and hydrophilic hydroxyl groups in the coating, leading to the formation of a mixed-mode stationary phase in the coating. This type of mixed- mode stationary phase may be employed for various uses, including, for example, retention of proteins and small molecules such as drugs under reverse phase and/or normal conditions in an SPE column.

[0062] The amine group is an extremely versatile chemical reagent with a rich chemistry. Information about some of these reactions may be found in United States Patent Application No. 12/040,638 filed on 29 February 2008, entitled, "Functionalized Diamond Particles And Methods For Preparing The Same," naming Matthew R. Linford and Gauray Saini as inventors, which is hereby incorporated herein, in its entirety, by this reference.

[0063] FIG. 2 describes another embodiment of a method 200 in which all or a portion of the acid-base-resistant shell particles are coated with polymer material prior to being adhered to the core particles or to each other (e.g., in a layer-by-layer process described above). Core particles may include any core shell particle material described herein, including a carbonized polymer or polymers, such as any polymer described herein which has been carbonized. In method 200, act 210 includes applying a polymer coating to acid-base-resistant shell particles to yield coated particles 214. In act 220, acid-base-resistant core particles 222 are mixed with the shell particles 212 using any suitable mixing process. The polymer coating on the coated shell particles 214 bonds the shell particles 212 to the core particles 222 to yield an intermediate composite particle 224. Additional layers of shell particles may be bonded to the intermediate composite particle 224 by adding a second portion of coated shell particles 214 or alternatively by coating the composite particles 224 with polymer material and shell particles as described in acts 1 10 and 120. The method 200 may also include additional curing and/or cross- linking acts as described above with regard to the method 100.

[0064] In one embodiment, the porous composite particulate material may include a body of bonded composite particles. The body may be formed by forming a bed of coated intermediate composite particles (e.g., composite particles 224) and polymerizing or otherwise joining the individual composite particles together to form a coherent body. Forming a body of bonded composite particles may allow the individual particles to maintain their integrity.

[0065] In other embodiments, some of the core particles may be coated with polymer material and some of the core particles may be uncoated. Also some of the shell particles may be coated with polymer material and some of the shell particles may be uncoated. In such an embodiment, the coated/uncoated core particles may be mixed together with the coated/uncoated shell particles to form a plurality of composite particles.

[0066] FIG. 3 describes a method for forming a body of bonded composite particles in vessel according to another embodiment. In this embodiment, a vessel 302 is provided that includes an inlet 304 and an outlet 306. A plurality of core particles are positioned within the vessel 302 to form a particle bed 308. The core particles may be retained in the vessel by a frit 310. In a first act, the vessel 302 is at least partially filled to form the bed 308. In a second act, the particles in the bed 308 are at least partially coated with a layer of polymer. In a third act, a suspension of shell particles is caused to flow through the bed 308, such as through voids between adjacent core particles. The shell particles bond to the core particles through the layer of polymer. Additional porous shell layers may be added as described above with regard to FIGS. 1 and 2. The body may be formed by curing and/or cross-linking the intermediate composite particles so- formed while packed in the vessel as a bed. The bonded composite particles have improved structural integrity, which may help prevent shell particles from being freed during use of the porous composite particulate material in chromatography.

[0067] In some embodiments, the shell particles may include at least some diamond particles, such as ultra-clean diamond particles (e.g., ultra-clean nano-scale diamond particles). Ultra-clean diamond particles may be made by subjecting diamond particles (e.g., UDD particles) to a cleaning process to reduce the total amount of metallic impurities thereof to less than about 40 ppm such as less than 1/4 of the amount present before any leaching process). In some embodiments, the cleaning process includes leaching the diamond particles in an acid, such as for example, an enhanced aqua regia solution (e.g., agua regia at about 90 °C), hydrofluoric acid, hydrochloric acid, or combinations thereof for a time sufficient to reduce the total amount of metallic impurities to about 40 ppm or less. Aqua regia includes hydrochloric acid and nitric acid at an approximately 3: 1 ratio. In an embodiment, diamond shell particles may be subjected to leaching in a hydrochloric acid and/or a hydrofluoric acid solution. Hydrochloric acid and/or hydrofluoric acid leaching solutions may be used in addition to and/or in combination with other acids or acid mixtures (e.g., an enhanced aqua regia leaching solution). The concentration of the leaching agent(s) (e.g., aqua regia, hydrochloric acid, hydrofluoric acid, and/or combinations of the foregoing) may range from about 1 M to about 25 M depending on the reagent and the desired leaching time and/or pH. For example, hydrochloric acid may be present in the leaching solution in a molar concentration from about 1 M to about 12.5 M, such as about 3 M to about 1 1 M. Hydrofluoric acid may be present in the leaching solution in an amount of about 1 M to about 25 M, such as about 3M to about 20 M.

[0068] The diamond particles (e.g., nano-scale diamond particles) may be leached in any of the solutions described herein for a time sufficient to render the diamond particles (e.g., the surface of the diamond particles) substantially free of metallic impurities (e.g., a diamond particle having total metallic impurity content of about 40 ppm or less). In some embodiments, suitable leaching times may be about 1 hour or more, such as about 1 hour to about 1 week, about 2 hours to about 24 hours, about 3 hours to about 12 hours, about 24 hours to about 96 hours, or about 48 hours. Further, the diamond particles may also be leached at elevated temperature and or pressures (e.g., enhanced leaching). For example the pressure in the leaching vessel and/or leaching chamber may be about 1 bar to about 500 bars. During leaching, the temperature in the leaching vessel and/or leaching chamber may be about 24 °C to about 500 °C. In some embodiments, any combination of leaching agents, leaching time, leaching temperature, and leaching pressure may be used to leach the diamond particles described herein. After leaching, the sp² hybridized carbon shell of the UDD particles may also be partially or substantially completely removed from the UDD particles, thereby leaving diamond particles consisting essentially of polycrystalline diamond with the total metallic impurity content discussed above.

[0069] Table 1 below lists the amount of each metallic impurity and the total amounts of metallic impurities present in diamond particles before and after respective leaching processes. All metallic impurity amounts are listed in parts per million (ppm). All of the diamond particles tested in Table 1 came from the same lot. A portion of the lot of diamond particles were tested without being leached to determine the metallic impurity content therein. Individual portions of the lot of diamond particles were cleaned using various leaching agents and techniques. As shown in Table 1, the total metallic impurity content of the as-received diamond particles was between about 89 ppm and about 92.5 ppm. The metallic impurities detected in the analysis of the diamond particles include aluminum, boron, cobalt, chromium, iron, magnesium, manganese, sodium, nickel, lead, silicon, and tungsten. The individual standard leaching processes tested included leaching in solutions of a modified HC1 mixture, hydrofluoric acid, sodium hydroxide, and DuPont aluminum cleaner respectively. The leaching processes included leaching in a relatively more acidic enhanced aqua regia ("Enhanced Aqua Regia #1"), Enhanced Aqua Regia #1 mixed with hydrochloric and hydrofluoric acids ("Enhanced Aqua Regia #1 + HCI/HF"), and a relatively concentrated enhanced aqua regia with leaching concentration and leaching temperature adjustments ("Enhanced Aqua Regia #2").

[0070] As demonstrated, the leaching processes using enhanced aqua regia resulted in metallic impurity contents of less than 1/4 of the original amount of the as- received diamond particles, and less than half of the metallic impurities left after even the best performing traditional leaching agents listed in Table 1 (e.g., the Modified HC1 mixture). For example, Enhanced Aqua Regia #1 caused over 75 % reduction of the metallic impurities over the as-received diamond particles. Enhanced Aqua Regia #2 caused over 85 % reduction of the metallic impurities from the as-received diamond particles. Enhanced Aqua Regia #1 + HCI/HF caused over a 90 % reduction of the metallic impurities from the as-recited diamond particles.

TABLE 1

[0071] The ultra-clean diamond particles leached using Enhanced Aqua Regia #1,

Enhanced Aqua Regia #1 + HC1/HF, and/or Enhanced Aqua Regia #2 exhibited total metallic impurity content— less than 20.6 ppm, less than 8.95 ppm, and less than 12.36 ppm respectively. Ultra-clean diamond particles having total metallic impurity content of less than 20.6 ppm were used to form the porous composite particles described herein. Ultra-clean diamond particles having a total metallic impurity content of less than about 40 ppm, less than about 30 ppm, less than about 20 ppm, or less than about 10 ppm may be particularly suitable for use in composite particles as described herein.

III. Porous Composite Particulate Materials

[0072] The porous composite particulate materials described herein provide desired sizes, porosity (e.g., pore volume), surface areas, and chemical stability suitable for chromatography and SPE techniques. When used in chromatography and SPE, high- resolution separation may be achieved with relatively low back pressure, which is in contrast to columns and cassettes that use high surface area particles without the composite structure described herein.

[0073] The porous composite particulate materials include a plurality of composite particles, with each composite particle including a core particle at least partially surrounded by one or more layers of shell particles. The shell particles are bonded to the core particles by a polymer coating. The core particles may be made from the acid-base- resistant materials described above, including but not limited to diamond particles, graphitic carbon, silicon carbide, boron nitride, tungsten carbide, carbonized polymer(s), or combinations of any of the foregoing. In some embodiments, the at least some of the shell particles may be diamond particles, such as ultra-clean nano-scale diamond particles. The porous composite particulate material may also have any combination of polymers described above. However, in an embodiment, the polymer coating that bonds the core particles to the shell particles and/or the shell particles to themselves is an amine polymer.

[0074] The composite particles may be provided in the form of finely divided discrete particles (e.g., a powder). Alternatively, the composite particles may be provided as a body of bonded composite particles. When the composite particles are provided as a body of bonded composite particles, the body may exhibit dimensions suitable for use in a separation apparatus, such as, but not limited to, separation devices used in HPLC.

[0075] In one embodiment, the composite particles have a particle size in a range from about 0.2 μιη to 500 μιη, more specifically about 1 μιη to 200 μιη, or even more specifically in a range from about 1 μιη to about 150 μιη. In one embodiment, the composite particles have a particle size in a range from about 1 μιη to about 10 μιη, or more specifically about 1.5 μιη to about 7 μιη. This particle range may be particularly useful for HPLC applications and the like. In another embodiment, the composite particles can have a particle size can be in a range from about 0.2 μιη to about 500 μιη, or more specifically in a range from about 10 μιη to about 150 μιη. This larger particle range may be more suitable for use in solid phase extraction applications and the like.

[0076] The composite particles may include a desired surface area. The surface area may depend on core and shell particle size, number of porous shell layers, and particle geometry. However, the surface area of the composite particles is higher than a similarly sized core particle due to the additional surface area provided by the shell particles. In an embodiment, the surface area may be measured using the Brunauer Emmett and Teller ("BET") technique and is in a range from 1-500 m²/g for composite particles having a particle size in a range from about 1 μιη to 500 μιη, more specifically in a range from 25- 300 m²/g, or even more specifically 50-200 m²/g. In one embodiment, the particle size range of the composite particles may be from about 1 μιη to 10 μιη and the surface area range from about 10-500 m²/g, more specifically from 25-200 m²/g, and even more specifically from 25-60 m²/g. In another embodiment, the particle size of the composite particles may be from about 10 μιη to 150 μιη and the surface area range may be from about 5-200 m²/g, or more specifically 10-100 m²/g. In yet another embodiment, the particle size the composite particles may range from about 250 μιη to about 500 μιη and the surface area may be least about 5 m²/g, and even more specifically at least about 10 m²/g, or more than 10 m²/g.

[0077] In a more detailed embodiment, a composite particle including a diamond (e.g., ultra-clean diamond) or a carbonized polymer core particle having a size of about 2.5 μιη to about 5 μιη and 1-50 porous shell layers of diamond shell particles having a particle size of about 5 nm to about 50 nm may have a surface area of about 1 m²/g to about 60 m²/g. In a more specific embodiment, a composite particle including a diamond or carbon polymer core particle having a size of about 2.5 μιη and 10-50 porous shell layers of diamond shell particles having a particle size of about 5 nm to about 10 nm may have a surface area of about 14 m²/g to about 60 m²/g. In another more specific embodiment, a composite particle including a carbonized polymer or diamond core particle having a size of about 5 μιη and 10-50 porous shell layers of diamond shell particles having a particle size of about 5 nm to about 10 nm may have a surface area of about 7 m²/g to about 33 m²/g.

[0078] FIG. 4 illustrates a composite particle that includes at least a bilayer of polymer according to another embodiment. A bilayer of polymer may be constructed from a first polymer coating 402 on an acid-base-resistant core particle 404. The polymer coating 402 may be formed using acts 1 10 and 210 as described above. A bilayer is formed by adding a functional polymer layer 406 and a second polymer coating layer 408. The polymer layers 402 and 408 are binding layers selected for bonding the shell particles to the core particles and/or the shell particles to the shell particles. The functional layer 406 is a polymeric layer that imparts a desired functionality to the composite particle. The polymers that are used to make the functional layer 406 may be selected from the polymers mentioned above that are useful for forming layers 402 and 408. However, the formation of a bilayer allows the selection of two or more different polymers to form the composite thereby allowing the different polymer layers to be optimized for different purposes. Typically, the layers 402 and 408 are selected for bonding inorganic polymers together and the functional polymer layer 406 is selected for providing a separate function such as, but not limited to properties related to separation efficiency. In one embodiment, the functional polymer layer 406 may be an anionic polymer.

[0079] In some embodiments, an additional particulate component may be embedded in the porous shell layers of the shell particles. The additional particulate component may be any organic or inorganic material that provides a desired property to the porous composite particulate material. In one embodiment, the additional component may be initially included in the manufacture of the composite particles but then removed. For example, the porous shell layers may include silica particles that exhibit a selectivity to be removed over more acid-base-resistant particles, such as diamond shell particles. This method may allow a composite particle to be formed with particular structural features. Alternatively, the additional component may be included with the purpose of removing or eluting out the component during use. For example, the additional component may be configured to elute out over time in the presence of a mobile phase.

[0080] In one embodiment, the additional component may be a particle that has affinity for a drug or other chemical reagent. In one embodiment, the additional component may include a catalytic reagent. The additional component may be included in the core particles and/or the layers of shell particles. IV. Separation Apparatuses and Methods

[0081] FIG. 5 is a cross-sectional view of a separation apparatus 500 according to an embodiment. The separation apparatus 500 may include a column 502 defining a reservoir 504. A porous body 506 (e.g., a porous composite bed, porous disk, other porous mass, etc.) may be disposed within at least a portion of the reservoir 504 of the column 502. The porous body 506 may comprise any of the porous composite particulate materials disclosed herein in bonded or powder form. The porous body 506 is porous so that a mobile phase may flow therethrough. In various embodiments, a frit 508 and/or a frit 510 may be disposed in column 502 on either side of porous body 506. The frits 508 and 510 may comprise any suitable material that allows passage of a mobile phase and any solutes present in the mobile phase, while preventing passage of the composite particulate material present in porous body 506. Examples of materials used to form the frits 508 and 510 include, without limitation, glass, polypropylene, polyethylene, stainless steel, polyether ether ketone ("PEEK"), titanium, polytetrafluoroethylene, or combinations thereof.

[0082] The column 502 may comprise any type of column or other device suitable for use in separation processes such as chromatography and solid phase extraction processes. Examples of the column 502 include, without limitation, chromatographic and solid phase extraction columns, tubes, syringes, cartridges (e.g., in-line cartridges), and plate containing multiple extraction wells (e.g., 96-well plates). The reservoir 504 may be defined within an interior portion of the column 502. The reservoir 504 may permit passage of various materials, including various solutions and solvents used in chromatographic and solid-phase extraction processes.

[0083] The porous body 506 may be disposed within at least a portion of reservoir 504 of the column 502 so that various solutions and solvents introduced into the column 502 contact at least a portion of the porous body 506. The porous body 506 may comprise a plurality of substantially non-porous particles in addition to the composite porous material.

[0084] In certain embodiments, frits, such as glass frits, may be positioned within the reservoir 504 to hold porous body 506 in place, while allowing passage of various materials such as solutions and solvents. In some embodiments, a frit may not be necessary, such as the body of bonded-together composite particles as described above with reference to FIG. 4. [0085] In one embodiment, the separation apparatus 500 is used to separate two or more components in a mobile phase by causing the mobile phase to flow through the porous body 506. The mobile phase is introduced through an inlet and causes the components to flow through the porous body 506 and the separated components may be recovered from the outlet 512.

[0086] In one embodiment, the mobile phase includes organic solvents, acids, or bases. In one embodiment, the mobile phase includes a concentrated acid with a pH less than about 3, more specifically less than about 2. In another embodiment, the mobile phase includes a base with a pH greater than about 10, more specifically greater than about 12, and even more particularly greater than 13.

[0087] In one embodiment, the separation apparatus 500 is washed between a plurality of different runs where samples of mixed components are separated. In one embodiment, the washing may be performed with water. In another embodiment, a harsh cleaning solvent is used. In this embodiment, the harsh cleaning solvent may be a concentrated organic solvent and/or a strong acid or base. In one embodiment, the cleaning solvent has a pH less than about 3, more specifically less than about 2. In another embodiment, the cleaning solvent has a pH greater than about 10, more specifically greater than about 12, and even more particularly greater than 13.

[0088]

V. WORKING EXAMPLES

[0089] The following examples are for illustrative purposes only and are not meant to be limiting with regards to the scope of the specification or the appended claims. For example, the present disclosure and claims are not limited to the use of diamond particles, unless otherwise specified.

Example 1: Synthesis Of Composite Diamond Particles

[0090] Example 1 describes the synthesis of core-shell composite particles using an amine polymer, micron-sized core carbonized polymer particles, and ultra-clean nanodiamond shell diamond particles.

[0091] Core-shell particles were synthesized using 15 nm shell particles comprising ultra-clean diamond exhibiting less than 20.6 ppm of metallic impurities thereon. The ultra-clean nanodiamond was formed by leaching UDD particles with enhanced aqua regia (e.g., aqua regia at elevated temperature such as 90 °C or more) and hydrofluoric acid. The core particle was a carbonized polymer particle of divinylbenzene ("DVB") having a generally spherical shape exhibiting a diameter of about 3.4 μιη. A layer of polyallylamine polymer was applied to the outside of the core particle. The ultra-clean nanodiamonds were applied over the polymer, and the process was repeated 10 times. The shell thickness was about 70 nm to about 133 nm. The core-shell particles were functionalized and cross-linked with a mixture of 1 ,2-epoxyoctadecane and 1,2,7,8- diepoxyoctane.

[0092] As shown in FIG. 6, a scanning electron microscope was used to image the core-shell particles of Working Example 1. The resulting core shell particles exhibit a substantially spherical outer shape having a plurality of ultra-clean nanodiamond particles and a polymer between the core particle and the outer surface of the core particle-shell.

[0093] Core-shell particles made according to Working Example 1 were tested for surface area Brunauer-Emmett-Teller ("BET") and pore volume using a Barrett-Joyner- Halenda ("BJH") pore size and volume analysis. The core-shell particles exhibited an average pore size of about 127 angstroms and a surface area of about 25.75 m²/g.

[0094] Porous silica particles exhibiting a diameter of about 3 μιη were also tested in a similar manner for comparison to the core-shell particles. The silica particles exhibited an average pore size of about 120 angstroms. As demonstrated in FIG. 7, and notwithstanding the difference in scale, the silica particles (upper graph) exhibited pore volume and pore diameter characteristics similar to Working Example 1 (lower graph). For example, both types of particles exhibited Gaussian adsorption distributions. The core-shell particle column according to Working Example 1 exhibited characteristic peaks at generally the same pore size having a generally similar tailing shape to that of the silica column. Thus, the ultra-clean nanodiamond-containing core-shell particles demonstrated suitability for chemical separations comparable to silica and further have a far superior chemical stability in harsh solutions (e.g., strongly basic or strongly acidic solutions).

[0095] FIGS. 8A-8D depict chromatograms made using HPLC columns having diamond containing core-shell particles. FIG. 8A is a side-by-side comparison of chromatograms made using an HPLC column having core-shell particles including diamond particles in the shell layers that were cleaned according to a conventional leaching process. In a control run (labeled "Control"), the diamond shell particles of the core-shell particles in the HPLC column were used as-is. In a masked run (labeled "Masked"), the diamond shell particles were subjected to a masking process using benzo(a)pyrene as an aromatic masking agent. The benzo(a)pyrene adheres (e.g., bonds and/or adsorbs) to the surface of the diamond material. Aromatic compounds (e.g., benzene, pyrene, anthracene, and/or chrysene) may be used to mask secondary interaction sites caused by metallic impurities, sp² carbon, or other adsorptive or reactive moieties on the surface of the diamond material in the shell particles. Secondary interaction sites are believed to cause increased tailing due to unintended interaction (e.g., reactivity and/or adsorption) of analytes at the sp² carbon or other moiety on the surface of the shell particle diamond. Typically, diamond materials (e.g., UDD) have many secondary interaction sites at the surface of the diamond particles. Such secondary interaction sites may result in tailing during chemical separations using HPLC columns having the diamond materials therein. Masking has been used to reduce tailing by occupying or otherwise blocking the secondary interaction sites at the surface of the diamond.

[0096] The HPLC columns tested were about 4.6 mm in diameter and about 33 mm in length. The mobile phase consisted of a 65:35 sequence of 1000 ml water with 4 ml of formic acid for an aqueous solvent and an organic solvent consisting of methanol with a flow rate of 0.800 ml/min. The column temperature was 35 °C and the detection was carried out at 280 nm. An analyte mixture containing a plurality of various parabens including methyl, ethyl, propyl, and butyl parabens was injected into the individual columns. As demonstrated in FIG. 8A, the masked column exhibited relatively high resolution (e.g., tall peaks), limited tailing, and faster elution times as compared to the control column. The inventors believe that this is due to unintended secondary interactions caused by the relatively high amount of impurities (e.g., metallic impurities and/or secondary interaction sites) in the conventionally cleaned diamond material used to make the HPLC columns. Thus, it may be necessary to mask the surface of conventionally cleaned (e.g., conventionally leached) diamond shell particles in an HPLC column to achieve a desired efficiency, resolution, tailing etc.

[0097] FIGS. 8B-8D depict chromatograms made using HPLC columns having core- shell particles according to Working Example 1. In the control sample, no aromatic compounds were applied to the core-shell particles. In the aromatic column, benzo(a)pyrene was applied (e.g., bonded and/or adsorbed) to the core-shell particles. To test whether the use of ultra-clean nanodiamond shell particles reduces tailing through the reduction of secondary reaction sites, two HPLC columns were made. One of the two HPLC columns included core-shell particles having the ultra-clean diamond shell particles that were masked (labeled as "aromatic") and the other HPLC column included core-shell particles having the ultra-clean diamond shell particles that were used as- is(labeled as "control"), as discussed above. The masking compound was benzo(a)pyrene. An analyte mixture containing a plurality of various parabens including methyl, ethyl, propyl, and butyl parabens was injected into the individual columns. The mobile phase consisted of a 60:40 sequence of 1000 ml water with 4 ml of formic acid for an aqueous solvent and an organic solvent consisting of methanol with a flow rate of 0.800 ml/min. The column temperature was 35 °C and the detection was carried out at 280 nm.

[0098] The resulting chromatograms, shown overlaid in FIG. 8B, show similar peak elution times and heights for both columns. As demonstrated in FIGS. 8C and 8D, the tailings in the two columns were substantially the same. In FIG. 8C, the tailing in the control column (i.e., the sample traditionally expected to have significant tailing due to secondary interaction sites) is almost identical in shape to the tailing in the aromatic column (i.e., the column expected to have minimal tailing due to masking) shown in FIG. 8D. When compared to FIG. 8A, a difference between the respective control columns is apparent. The column made using ultra-clean nanodiamond (FIGS. 8B-8C) exhibits separation characteristics substantially similar to the masked column, whereas the column made with conventionally cleaned diamond (FIG. 8A) exhibited poor resolution, efficiency, and tailing compared to the masked column. The inventors currently believe that the lack of difference (e.g., in tailing, resolution, efficiency) between the masked and unmasked ultra-clean diamond surfaces is due to the fact that the ultra-clean nanodiamond particles have significantly fewer secondary interaction sites than diamond material leached according to conventional processes, thus eliminating the need for masking.

[0099] FIGS. 9A and 9B show HPLC chromatograms from an HPLC column made using core-shell particles according to Working Example 1. The HPLC column was 4.6 mm in diameter and about 33 mm in length. Referring to FIG. 9A, the analytes tested were a mixture of acidic herbicides. The mobile phase consisted of a 10:90 sequence of 100: 1.5 water to formic acid aqueous solvent and 100: 1.5 acetonitrile to formic acid organic solvent. The flow rate was 1,000 ml/min, the pressure was 740 psi and the temperature was 35 °C. The injection volume was 0.5 μΐ with 13 injections taking place. The resulting chromatogram shows distinct peaks having satisfactory resolution between peaks. The peaks have a generally Gaussian shape with relatively little tailing.

[00100] Referring to FIG. 9B, the analyte tested was a mixture of alkyl benzenes. The mobile phase consisted of a 50:50 sequence of 10 mM sodium phosphate buffer aqueous solvent and acetonitrile solvent. The flow rate was 1,000 ml/min, and the temperature was 35 °C. The injection volume was 2.0 μΐ with 7 injections taking place. The resulting chromatogram shows distinct peaks having satisfactory resolution between peaks. The peaks have a generally Gaussian shape with relatively little tailing.

[00101] FIGS. 7-9B demonstrate that HPLC columns having core-shell particles including ultra-clean diamond shell particles are suitable for chemical separations and particularly suitable for chemical separations including harsh chemicals (e.g., strong acids or strong bases).

[00102] While various aspects and embodiments have been disclosed herein, other aspects and embodiments are contemplated. The various aspects and embodiments disclosed herein are for purposes of illustration and are not intended to be limiting. Additionally, the words "including," "having," and variants thereof (e.g., "includes" and "has") as used herein, including the claims, shall be open ended and have the same meaning as the word "comprising" and variants thereof (e.g., "comprise" and "comprises").

Claims

CLAIMS What is claimed is:

1. A method for manufacturing a porous composite particulate material, comprising:

providing a plurality of acid-base-resistant core particles and a plurality of acid- base-resistant shell particles, at least a portion of the plurality of acid-base resistant shell particles including diamond particles exhibiting a total metallic impurity content of about 40 ppm or less;

coating at least a portion of the plurality of acid-base-resistant core particles, at least a portion of the plurality of acid-base-resistant shell particles, or combinations thereof with polymer material; and

adhering a portion of the plurality of acid-base-resistant shell particles to each of the plurality of acid-base-resistant core particles with the polymer material to form a plurality of composite particles.

2. The method of claim 1, wherein the plurality of acid-base-resistant shell particles of each composite particle forms a plurality of porous shell layers.

3. The method of claim 1, wherein the total metallic impurity content of the diamond particles is about 21 ppm or less.

4. The method of claim 1, wherein the total metallic impurity content of the diamond particles is about 10 ppm or less.

5. The method of claim 1, wherein at least a portion of the diamond particles includes polycrystalline diamond.

6. The method of claim 1, wherein the plurality of acid-base-resistant core particles exhibits a particle size of at least an order of magnitude larger than the plurality of acid-base-resistant shell particles.

7. The method of claim 1, wherein the polymer material is coated on the at least a portion of the plurality of acid-base-resistant shell particles before the act of adhering.

8. The method of claim 1, wherein the polymer material is coated on the at least a portion of the plurality of acid-base-resistant core particles before the act of adhering.

9. The method of claim 1, wherein the acts of coating and adhering include: immersing the plurality of acid-base-resistant core particles in a polymer solution to form polymer-functionalized core particles;

immersing the polymer-functionalized core particles in a suspension of a first portion of the plurality of shell particles to yield a plurality of intermediate composite particles;

immersing the intermediate composite particles in a polymer solution to yield polymer-functionalized intermediate composite particles; and

immersing the polymer-functionalized intermediate composite particles in a second portion of the plurality of acid-base-resistant shell particles to yield the composite particles.

10. The method of claim 1, further comprising bonding the plurality of the composite particles together.

1 1. The method of claim 1, wherein the acts of coating and adhering comprise: forming a bed of the plurality of acid-base-resistant core particles in a vessel; flowing a liquid polymeric material through the bed to coat the plurality of acid- base-resistant core particles thereof with the polymer material; and

flowing the plurality of acid-base-resistant shell particles through the bed to adhere the portion of the plurality of acid-base-resistant shell particles to the each of the plurality of acid-base-resistant core particles.

12. The method of claim 1, further comprising at least one of curing or cross- linking the polymer material after the act of adhering.

13. A porous composite particulate material, comprising:

a plurality of composite particles, each of the plurality of composite particles including:

an acid-base-resistant core particle;

a plurality of acid-base-resistant shell particles, at least portion of the plurality of acid-base-resistant shell particles including diamond particles exhibiting a total metallic impurity content of about 40 ppm or less; and

a polymer bonding the plurality of shell particles to the acid-base-resistant core particle.

14. The porous composite particulate material as in claim 13, wherein at least a portion of the plurality of acid-base-resistant shell particles includes at least one member selected from the group consisting of graphitic carbon, diamond, tungsten carbide, and boron nitride.

15. The porous composite particulate material of claim 13, wherein the polymer includes at least one amine polymer.

16. The porous composite particulate material of claim 13, wherein the polymer is at least partially cross-linked.

17. The porous composite particulate material of claim 13, wherein the total metallic impurity content of the diamond particles is about 30 ppm or less.

18. The porous composite particulate material of claim 13, wherein the total metallic impurity content of the diamond particles is about 21 ppm or less.

19. The porous composite particulate material of claim 13, wherein the total metallic impurity content the diamond particles is about 10 ppm or less.

20. A method of separating components, comprising:

placing the porous composite particulate material according to any one of claims 13-19 in a vessel;

providing a mobile phase including at least two different components to be separated; and

flowing the mobile phase through the porous composite particulate material to physically separate the at least two different components.