A porous material having a controlled porosity for chromatographic separation; a preparation method thereof; and uses thereof

Abstract

The present invention provides a porous material having controlled porosity for chromatographic separations, a process for its preparation and its use. The present invention provides novel chromatographic materials, for example for chromatographic separations, methods for their preparation, and separation devices comprising the chromatographic materials. The chromatographic material of the present invention has a controlled porosity and comprises a chromatographic core material and one or more layers of chromatographic surface material, the layers each independently providing an average pore size, average pore volume, or specific surface area such that the combined layers form the chromatographic material having a predetermined or desired porous pattern from the core material to the outermost surface. The material can be used for HPLC separation, normal phase separation, reverse phase separation, chiral separation, HILIC separation, SFC separation, affinity separation, perfusion separation, partial perfusion separation, and SEC separation.

Description

[0001] This application is a divisional application of the invention application filed on March 6, 2017, with Chinese national application number 201780028131.2, entitled "Porous material with controlled porosity for chromatographic separation; preparation method thereof; and use thereof". Technical Field

[0002] This invention relates to the fields of chromatographic materials and chromatographic separation. Background Technology

[0003] Packing materials used in liquid chromatography (LC) are generally classified into two categories: organic materials, such as polyvinylbenzene; and inorganic materials, with silica being a typical example. Many organic materials are chemically stable to both strongly basic and strongly acidic mobile phases, allowing for flexibility in mobile phase pH selection. However, organic chromatographic materials often result in lower column efficiency, especially for low molecular weight analytes. Many organic chromatographic materials not only lack the mechanical strength of typical chromatographic silica but also shrink and swell when the composition of the mobile phase changes.

[0004] Silica is the most widely used material in high-performance liquid chromatography (HPLC), ultra-high-performance liquid chromatography (UPLC), and supercritical fluid chromatography (SFC). The most common applications utilize silica surface-derived from organic functional groups such as octadecyl (C18), octyl (C8), phenyl, amino, and cyano groups. As stationary phases in HPLC, these packing materials result in highly efficient columns with no signs of shrinkage or swelling.

[0005] Current hybrid material technology (HMT) offers a significant solution to the traditional chromatographic problems encountered with silica-based packed materials. HMT improvements include significantly improved high pH stability and excellent low pH stability, good mechanical stability, good peak shape at pH 7, higher efficiency, good retention, and desired chromatographic selectivity.

[0006] In the 1970s, surface porous particles (also known as thin-film fused-core or core-shell particles) were commonly used as chromatographic adsorbents. These early surface porous materials consisted of a thin porous layer formed by adsorption of silica sol onto the surface of an undefined, polydisperse, nonporous silica core (>20 µm). Processes typically involved spraying or flowing a sol solution through a particle bed. Kirkland extensively explored the use of surface porous particles during this period and helped develop the Zipax brand of surface porous materials. A review of Kirkland's career is provided by Unger (…). Journal of Chromatography A , 1060 (2004) 1) Provided.

[0007] Surface porous particles have been an extremely active research area over the past five years. This includes both fully porous (EP 84, 979 B1, 1996) and surface porous particles (…). Advanced Materials 1998, 10 Both, 1036), use a mixture of condensed tetraalkoxysilanes and YSi(OR)3 type (where Y contains an alkyl or aryl group and R is methoxy or ethoxy) organosilanes. A previous report has been made by Unger. These particles do not have a size (1µm-2µm) sufficient for effective use in UPLC, nor do they contain pore geometry features that enhance chromatography. Narrowly distributed surface porous particles have been reported by Kirkland (US Application 20070189944) using a layer-by-layer (LBL) method—however, these particles are not highly spherical. Other surfactant-templated methods yield narrowly distributed, fully porous particles in low yields; however, these methods have not yet been used to prepare monodisperse spherical surface porous particles with pore geometry features that enhance chromatography.

[0008] Currently available commercially available surface-porous particles utilize small (<2µm) monodisperse spherical high-purity non-porous silica cores. A porous layer is formed, allowing these particles to grow to a final diameter of 1.7µm-2.7µm. The thickness and pore size of the porous layer are optimized for specific applications (e.g., smaller...). vs. (Separation of larger molecules). To remove polymeric electrolytes, surfactants, or binders (additional reagents added during synthesis) and to strengthen the particles for HPLC or UPLC applications, these materials are calcined (500-1000°C in air). Additional pore-enlarging, acid treatment, re-hydroxylation, and bonding steps have been reported.

[0009] Evaluations of surface-porous materials (e.g., Journal of Chromatography A, 1217 (2010) 1604-1615; Journal of Chromatography A, 1217 (2010) 1589-1603) indicate that improvements in column performance can be achieved using columns filled with these surface-porous materials. While not limited by theory, improvements are noted in van der Munther clauses and improved thermal conductivity. A recent patent application from the University of Cork also relates to surface-porous particles (WO 2010 / 061367 A2).

[0010] While these reported surface porous particle processes differ, they can be categorized into those involving the formation of pre-formed sol layers (e.g., the AMT method) or growth using high-purity tetraalkyloxysilane monomers (e.g., the University College Cork method). The AMT and University College Cork methods share the characteristic of utilizing centrifugation followed by re-dispersion to introduce post-processing in repeated processes (more than nine times). For the AMT method, this is necessary for a layer-by-layer approach applying alternating layers of positively charged polymeric electrolytes and negatively charged silica sols. For the University College Cork method, post-processing is used to reduce re-crystallization and agglomeration events. FIB / SEM analysis revealed particles with smooth particle surfaces and significant layer formation. Although both methods use similar spherical monodisperse silica cores with particle sizes increasing with the number of porous layers, they differ in the final particle morphology of the surface porous particles. The AMT method results in uneven surface features and variations in porous layer thickness. This difference in surface morphology is likely due to variations in the initial sol-forming layers. Most notably, both methods utilize high-temperature heat treatment in air to remove additives (polymeric electrolytes or surfactants) and improve the mechanical properties of their surface porous particles. Because hybrid materials are thermally unstable above 600°C, this method is not suitable for forming hybrid surface porous particles.

[0011] The narrow-size porous chromatographic particles to be synthesized are expected to be highly beneficial for chromatographic separation. These particles should exhibit an optimal balance between column efficiency and back pressure.

[0012] Although descriptions of monodisperse surface porous silica particles have been mentioned in the literature, these particles have not demonstrated chromatographically beneficial pore geometry and controlled pore size for various chromatographic applications.

[0013] Therefore, there is still a need for a method in which filling materials, including fully porous and surface porous materials, can be prepared with controlled and desired pore sizes and pore geometry features that enhance chromatography.

[0014] Similarly, there is still a need for a method to prepare porous materials with controlled porosity and improved chemical stability in high-pH mobile phases. Summary of the Invention

[0015] The present invention provides, for example, novel chromatographic materials for chromatographic separation, methods for their preparation, and separation apparatus comprising the chromatographic materials.

[0016] In one aspect, the present invention provides chromatographic materials with controlled porosity. In some embodiments, the chromatographic material with controlled porosity is in the form of particles, a solid mass, or a surface-porous material. In other embodiments, the chromatographic material of the present invention has pore geometry features that enhance chromatographic performance. In some specific embodiments, the chromatographic material of the present invention does not have pore geometry features that enhance chromatographic performance.

[0017] In another aspect, the present invention provides a chromatographic material with controlled porosity, comprising a chromatographic core material having a main surface and one or more chromatographic surface materials.

[0018] In some embodiments, the chromatographic core material having a main surface of the material of the present invention is a non-porous material, a substantially non-porous material, a surface-porous material, or a fully porous material. In specific embodiments, the chromatographic core material is an inorganic material, an organic material, or an inorganic / organic hybrid material. In other specific embodiments, the chromatographic core material is an inorganic material; silica; silica coated with an inorganic / organic hybrid surrounding material; a magnetic core material; a magnetic core material coated with silica; a high thermal conductivity core material; a high thermal conductivity core material coated with silica; a composite material; an inorganic / organic hybrid surrounding material; a composite material coated with silica; a magnetic core material coated with an inorganic / organic hybrid surrounding material; or a high thermal conductivity core material coated with an inorganic / organic hybrid surrounding material. In some embodiments, the chromatographic core material is not a hollow core material.

[0019] In some embodiments, the chromatographic core material having the main surface of the material of the present invention has the formula: (SiO2) d / [R 2 ((R) p (R 1 ) q SiO t ) m (I) in, R and R 1 Each independently is C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C18 Alkyl, C2-C 18 Alkenyl, C2-C 18 Alkynyl, C3-C 18 Cycloalkyl, C1-C 18 Heterocycloalkyl, C5-C 18 Aryl, C1-C 18 Heteroaryl; or absent; wherein each R 2 is connected to two or more silicon atoms; p and q are each independently 0.0 to 3.0, t is 0.5, 1.0, or 1.5; d is 0 to about 30; m is an integer from 1 to 20; wherein R, R 1 and R 2 are optionally substituted; Provided that: (1) when R 2 is absent, m = 1, and when 0 < p + q ≤ 3, ; and (2) when R 2 is present, m = 2 to 20, and when p + q ≤ 2, ; Formula: (SiO2) d / [(R) p (R 1 ) q SiO t (II) Wherein, R and R 1 are each independently C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 Alkenyl, C2-C 18 Alkynyl, C3-C 18 Cycloalkyl, C1-C 18 Heterocycloalkyl, C5-C 18 Aryl, C5-C 18 Aryloxy, or C1-C 18 Heteroaryl; d is 0 to about 30; p and q are each independently 0.0 to 3.0, provided that when p + q = 1, then t = 1.5; when p + q = 2, then t = 1; or when p + q = 3, then t = 0.5; Formula: (SiO2) d / [R 2 ((R1 ) r SiO t ) m (III) in, R 1 For C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C1-C 18 heteroaryl; or nonexistent; where each R 2 Connected to two or more silicon atoms; d ranges from 0 to approximately 30; r can be 0, 1, or 2, provided that when r=0, then t=1.5; when r=1, then t=1; or when r=2, then t=0.5. and m is an integer from 1 to 20; Mode: (A) x (B) y (C) z (IV) The repeating units A, B, and C can be arranged randomly, block, or a combination of random and block; A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit bonded to one or more repeating units B or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds; C is an inorganic repeating unit bonded to one or more repeating units B or C via inorganic bonds; x and y are positive numbers, and z is a non-negative number, where x + y + z = 1. In some embodiments, z = 0, then 0.002 ≤ x / y ≤ 210, and when z ≠ 0, then 0.0003 ≤ y / z ≤ 500 and 0.002 ≤ x / (y + z) ≤ 210; or Mode: (A) x (B) y (B*) y* (C) z (V) The repeating units A, B, B*, and C can be arranged randomly, block, or a combination of random and block; A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit bonded to one or more repeating units B or B* or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds; B* is an organosiloxane repeating unit bonded to one or more repeating units B or B* or C via inorganic siloxane bonds, wherein B* is an organosiloxane repeating unit that is non-reactive (i.e., polymerizable) organic component and may further have protected functional groups that can be deprotected after polymerization; C is an inorganic repeating unit bonded to one or more repeating units B or B* or C via inorganic bonds; x and y are positive numbers, and z is a non-negative number, where x + y + z = 1. In some embodiments, when z = 0, then 0.002 ≤ x / (y + y*) ≤ 210, and when z = 0, then 0.002 ≤ x / (y + y*) ≤ 210. When x ≠ 0, then 0.0003 ≤ (y + y*) / z ≤ 500 and 0.002 ≤ x / (y + y* + z) ≤ 210.

[0020] In some embodiments of the invention, each layer of one or more chromatographic surface materials independently comprises one or more nanoparticles. In some embodiments, each nanoparticle is independently an inorganic material or an inorganic / organic hybrid material. In other embodiments, each nanoparticle is independently an oxide or nitride of diamond, carbon black, graphite, carbon nanotubes, silicon carbide, or aluminum, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, or boron. In still other embodiments, each nanoparticle is independently a material having the following formula: (SiO2) d / [R 2 ((R) p (R 1 ) q SiO t ) m (I) in, R and R 1 Each independently is C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18Alkenyl, C2-C 18 Alkynyl, C3-C 18 Cycloalkyl, C1-C 18 Heterocycloalkyl, C5-C 18 Aryl, C5-C 18 Aryloxy, or C1-C 18 Heteroaryl; R 2 is C1-C 18 Alkyl, C2-C 18 Alkenyl, C2-C 18 Alkynyl, C3-C 18 Cycloalkyl, C1-C 18 Heterocycloalkyl, C5-C 18 Aryl, C1-C 18 Heteroaryl; or is absent; wherein each R 2 is connected to two or more silicon atoms; p and q are each independently 0.0 to 3.0, t is 0.5, 1.0, or 1.5; d is 0 to about 30; [[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​ d ranges from 0 to approximately 30; p and q are each independently between 0.0 and 3.0, provided that when p+q=1, then t=1.5; when p+q=2, then t=1; or when p+q=3, then t=0.5. Mode: (SiO2) d / [R 2 ((R 1 ) r SiO t ) m (III) in, R 1 For C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C1-C 18 heteroaryl; or nonexistent; where each R 2 Connected to two or more silicon atoms; d ranges from 0 to approximately 30; r can be 0, 1, or 2, provided that when r=0, then t=1.5; when r=1, then t=1; or when r=2, then t=0.5. and m is an integer from 1 to 20; Mode: (A) x (B) y (C) z (IV) The repeating units A, B, and C can be arranged randomly, block, or a combination of random and block; A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit bonded to one or more repeating units B or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds; C is an inorganic repeating unit bonded to one or more repeating units B or C via inorganic bonds; x and y are positive numbers, and z is a non-negative number, where x + y + z = 1. In some embodiments, z = 0, then 0.002 ≤ x / y ≤ 210, and when z ≠ 0, then 0.0003 ≤ y / z ≤ 500 and 0.002 ≤ x / (y + z) ≤ 210; or Mode: (A) x (B) y (B*) y* (C) z (V) The repeating units A, B, B*, and C can be arranged randomly, block, or a combination of random and block; A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit bonded to one or more repeating units B or B* or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds; B* is an organosiloxane repeating unit bonded to one or more repeating units B or B* or C via inorganic siloxane bonds, wherein B* is an organosiloxane repeating unit that is a non-reactive (i.e., polymerizable) organic component and may further have protected functional groups that can be deprotected after polymerization; C is an inorganic repeating unit bonded to one or more repeating units B or B* or C via inorganic bonds; x and y are positive numbers, and z is a non-negative number, where x+y+z=1. In some implementations, when z=0, then 0.002≤x / (y+y*)≤210, and when z ≠ 0, then 0.0003≤(y+y*) / z≤500 and 0.002≤x / (y+y*+z)≤210.

[0021] In some implementations, the materials used in the various layers of the chromatographic surface material may be a mixture of more than one type of material.

[0022] In a particular embodiment, each of the one or more nanoparticles has an average diameter of 1 nm to 400 nm or 5 nm to 200 nm.

[0023] In some embodiments, each layer of one or more chromatographic surface materials independently comprises two or more types of nanoparticles with different average diameters. In a particular embodiment, each layer independently comprises nanoparticles with different average diameters, wherein the two different average diameters are a larger average diameter and a smaller average diameter. In a specific embodiment, the diameter ratio of nanoparticles with a larger average diameter to nanoparticles with a smaller average diameter in each layer is independently greater than 1.75; in the range of 1.75 to 100, or in the range of 2 to 50. In other specific embodiments, the weight ratio of nanoparticles with a larger average diameter to nanoparticles with a smaller average diameter in each layer is independently from about 19:1 to 0.05:1; from about 15:1 to about 0.25:1; or from about 10:1 to about 0.5:1.

[0024] In other embodiments, each layer of one or more chromatographic surface materials independently has an average pore size of 20 angstroms to 1500 angstroms. In still other embodiments, the average pore size of one or more chromatographic surface materials varies from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material in a predetermined pattern. In specific embodiments, the predetermined pattern includes: an increase in average pore size from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material; a decrease in average pore size from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material; an increase in average pore size from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material; and a decrease in average pore size from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material.

[0025] In other embodiments, each layer of one or more chromatographic surface materials independently has a thickness of 25 μm. 2 / g to 1100m 2 The specific surface area is / g. In other embodiments, the specific surface area of ​​one or more layers of chromatographic surface material varies from the main surface of the chromatographic core material to the outermost surface of the chromatographic material in a predetermined pattern. In a particular embodiment, the predetermined pattern includes an increase in specific surface area from the main surface of the chromatographic core material to the outermost surface of the chromatographic material; a decrease in specific surface area from the main surface of the chromatographic core material to the outermost surface of the chromatographic material; or an increase in specific surface area from the main surface of the chromatographic core material to the outermost surface of the chromatographic material, and a decrease in specific surface area from the main surface of the chromatographic core material to the outermost surface of the chromatographic material.

[0026] In other embodiments, each layer of one or more chromatographic surface materials independently has a thickness of 0.15 cm. 3 / g to 1.5cm 3 / g average pore volume. In other embodiments, the average pore volume of one or more layers of chromatographic surface material varies from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material in a predetermined pattern. In a particular embodiment, the predetermined pattern includes an increase in average pore volume from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material; a decrease in average pore volume from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material; or an increase in average pore volume from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material, and a decrease in average pore volume from the main surface of the chromatographic core material to the outermost surface of the chromatographic core material.

[0027] In some implementations, the predetermined pattern includes variations in two or more of the following: average pore diameter, average pore volume, or specific surface area. Specifically, the predetermined pattern can be developed to produce a desired pore shape or desired properties at specific locations within the pore.

[0028] In some embodiments, at least one layer of one or more chromatographic surface materials is an inorganic / organic hybrid material comprising hydrophobic surface groups and one or more ionizable modifiers. In such embodiments, each ionizable modifier independently comprises a carboxylic acid group, a sulfonic acid group, an aryl sulfonic acid group, a phosphate group, a boric acid group, an amino group, an imino group, an amide group, a pyridyl group, an imidazolyl group, a urea group, a thionyl-urea group, or an aminosilyl group. In certain such embodiments, each ionizable modifier is independently derived from an ionizable modifier reagent selected from groups having the following formula: Formula (I) Equation (II): Equation (III): Or a combination of them, in m is an integer from 1 to 8; v is 0 or 1; When v is 0, m' is 0; When v is 1, m' is an integer from 1 to 8; Z represents a chemically reactive group, including (but not limited to) [a specific group]. -OH, -OR 6 Amines, alkylamines, dialkylamines, isocyanates, acyl chlorides, trifluoromethanesulfonates, isocyanates, thiocyanates, imidazole carbonates, NHS-esters, carboxylic acids, esters, epoxides, alkynes, alkenes, azides, -Br, -Cl, or -I; Y represents an embedded polar functional group; R 1Each occurrence independently represents a chemically reactive group on silicon, including (but not limited to) -H, -OH, -OR. 6 Dialkylamines, trifluoromethanesulfonates, Br, Cl, I, vinyl groups, alkenes, or -(CH2) m” Q; Q is -OH or -OR each time it appears. 6 Amines, alkylamines, dialkylamines, isocyanates, acyl chlorides, trifluoromethanesulfonates, isocyanates, thiocyanates, imidazole carbonates, NHS-esters, carboxylic acids, esters, epoxides, alkynes, alkenes, azides, -Br, -Cl, or -I; "m" is an integer from 1 to 8; p is an integer from 1 to 3; R 1’ Each occurrence is independently represented by F, C1-C. 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Heteroaryl, fluoroalkyl, or fluoroaryl; R 2 R 2’ R 3 and R 3’ Each time it appears, it independently represents hydrogen, C1-C. 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C2-C 18 Heterocyclic alkyl, C5-C 18 Acyl group, C5-C 18 aryloxy group, or C4-C 18 heteroaryl, -Z, or having the formula -Si(R') b R” a Or -C(R') b R” a group; a and b each represent integers from 0 to 3, provided that a + b = 3; R' represents a C1-C6 straight-chain, cyclic, or branched alkyl group; R” is a functionalized group selected from alkyl, alkenyl, alkynyl, aryl, cyano, amino, glycol, nitro, ester, cationic or anion exchange group, or an alkyl or aryl group containing an embedded polar functional group and a chiral moiety. R4 Indicates hydrogen, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 5 Indicates hydrogen, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 6 Each occurrence is represented independently as C1-C. 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; Het represents a heterocyclic or heteroaryl ring system containing at least one nitrogen atom; and A represents either the acidic ionizable modifier portion or the doubly charged ionizable modifier portion.

[0029] In such embodiments, the molar ratio of hydrophobic surface groups to ionizable modifier is about 2.5:1 to about 350:1; about 3:1 to about 200:1; or about 4:1 to about 35:1. In other embodiments, the concentration of ionizable modifier is less than about 0.5 µmol / m 2 Less than approximately 0.4 µmol / m 2 Less than approximately 0.3 µmol / m 2 Approximately 0.01 µmol / m 2 To approximately 0.5 µmol / m 2 Approximately 0.01 µmol / m 2 To approximately 0.4 µmol / m 2 Or approximately 0.03 µmol / m 2 To approximately 0.3 µmol / m 2 .

[0030] In other embodiments, the chromatographic material of the present invention has a density of approximately 25 μm. 2 / g to 1100m 2 / g; approximately 80m 2 / g to 500m 2 / g; or approximately 120m 2 / g to 330m 2 / g of surface area.

[0031] In other embodiments, the chromatographic material of the present invention has a diameter of about 0.15 cm. 3 / g to 1.7cm 3 / g; or approximately 0.5cm 3 / g to 1.3cm 3 / g pore volume.

[0032] In other embodiments, the chromatographic material of the present invention has a particle size of less than about 110 μm. 2 / g; less than approximately 105m 2 / g; less than approximately 80m 2 / g; less than approximately 50m 2 / g microporous surface area.

[0033] In other embodiments, the chromatographic material of the present invention has an average pore size of about 20 Å to 1500 Å; about 50 Å to 1000 Å; about 100 Å to 750 Å; about 110 Å to 500 Å; about 100 Å to 750 Å; or about 110 Å to 500 Å.

[0034] In other embodiments, the ratio of the core diameter to the particle diameter of the chromatographic material of the present invention (wherein the material is a particle having a chromatographic core) is 0.05 to 0.99; or 0.2 to 0.95.

[0035] In a particular embodiment, the chromatographic material of the present invention (the chromatographic material according to claim 1) is hydrolyzed stable at a pH of about 1 to about 14; about 10 to about 14; or about 1 to about 5.

[0036] In some embodiments, the chromatographic material of the present invention further includes surface modification. In specific embodiments, the material is surface modified by: coating polymer; by a combination of organic group and silanol group modification; by a combination of organic group modification and coating polymer; by a combination of silanol group modification and coating polymer; via forming organic covalent bonds between the organic groups of the material and the modifying agent; or by a combination of organic group modification, silanol group modification and coating polymer.

[0037] In another aspect, the present invention provides a separation apparatus having a stationary phase comprising the chromatographic material of the present invention. In some embodiments, the apparatus is selected from chromatographic columns, thin-layer plates, filter membranes, microfluidic separation devices, sample purification devices, solid supports, microchip separation devices, and microtiter plates. In other embodiments, the separation apparatus can be used for applications selected from: solid-phase extraction, high-performance liquid chromatography, combinatorial chemistry, synthesis, bioassay, ultra-high performance liquid chromatography, ultrafast liquid chromatography, ultra-high pressure liquid chromatography, supercritical fluid chromatography, and mass spectrometry.

[0038] In another aspect, the present invention provides a chromatographic column comprising: a) A column with a cylindrical interior for receiving filling material, and b) A packed chromatography bed containing the chromatographic material of the present invention.

[0039] In another aspect, the present invention provides a kit comprising the chromatographic material of the present invention and an instruction manual. In some embodiments, the instruction manual is intended for use with separation equipment, including but not limited to: chromatographic columns, thin-layer plates, microfluidic separation devices, filter membranes, sample purification devices, and microtiter plates.

[0040] In another aspect, the present invention provides a chromatographic apparatus comprising: a) Internal channels for receiving filling material, and b) A packed chromatography bed containing the chromatographic material of the present invention.

[0041] In one aspect, the present invention provides a method for preparing chromatographic materials according to the present invention, comprising the following steps: a. Provide chromatographic core materials with a main surface; and b. Apply one or more layers of chromatographic surface material to the main surface. To produce chromatographic materials with controlled porosity.

[0042] In another aspect, the present invention provides a method for preparing chromatographic materials according to the present invention, comprising the following steps: a. Provide chromatographic core materials with a main surface; and b. Apply a chromatographic surface material and an electrolyte to the surface; c. Removing the polymeric electrolyte to form the resulting material with a surface; and d. Optionally repeat steps b and c once or more on the surface of the resulting material. To produce chromatographic materials with controlled porosity.

[0043] In certain embodiments utilizing polymeric electrolytes, each polymeric electrolyte is independently a straight-chain, branched, or block polymer comprising one or more alkyl, cycloalkyl, aryl, or ethylene oxide groups and one or more primary, secondary, tertiary, and quaternary amino groups, pyrrolidone groups, pyridine groups, or imidazole groups, wherein each polymeric electrolyte may be positively or negatively charged. In such embodiments, the polymeric electrolyte is removed by calcination, heat treatment, chemical extraction, degradation, ozone decomposition, or a combination thereof.

[0044] In other embodiments, the method of the present invention further includes a post-synthesis processing step. In such embodiments, the post-synthesis processing step includes end-capping, hydrothermal treatment, extraction, ozone decomposition, lyophilization, pseudomorphic conversion, chromatographic material in an inorganic surrounding material, chromatographic material in an inorganic / organic hybrid surrounding material, drying, heat treatment, dispersion, acid treatment, reaction with hybrid functional groups, surface modification, grinding, fractionation, sedimentation, or a combination thereof.

[0045] In another aspect, the present invention provides a kit comprising the porous surface material of the present invention and an instruction manual. In some embodiments, the instruction manual is intended for use with a separation device. In some other embodiments, the separation device is selected from chromatographic columns, thin-layer plates, microfluidic separation devices, solid-phase extraction devices, filter membranes, sample purification devices, and microtiter plates. Attached Figure Description

[0046] Figure 1 The cross-sectional geometry of surface-porous and fully porous particles is shown, where c = particle center; d = core diameter; d' = particle diameter; 1 = particle radius; 0 = pore initiation along the radius; 1 = outer surface along the radius.

[0047] Figure 2 The diagram shows the distribution of physical properties of a representative selection of surface porous materials with normalized surface area (SA, left) and normalized pore size (PD, right) along the particle radius (1). Solid lines represent planned changes in surface area and pore size from the non-porous particle core to the outer particle surface. Dashed lines represent deviations in pore properties near the non-porous core surface.

[0048] Figure 3 The specific surface area (SSA) of silica nanoparticles is shown using Equation 2.

[0049] Figure 4 The estimates of the core weight fraction of different surface porous silica materials based on the core diameter to particle diameter ratio (Rho) are shown.

[0050] Figure 5Estimates for the synthesis of surface-porous silica materials (SSA) using different silica nanoparticles and Rho values ​​of 0.73 or 0.90 are shown. This method assumes a single nanoparticle feed for forming the porous layer.

[0051] Figure 6 Estimates for surface porous silica materials (SSA) using different silica nanoparticles (5 nm to 30 nm) and different Rho values ​​are shown. This method assumes a single nanoparticle feed for forming the porous layer.

[0052] Figure 7 This paper presents estimates of the average pore size (APD) of porous silica materials with different surfaces based on different silica nanoparticles. The method assumes a single nanoparticle feed for forming the porous layer. (The paper also includes APD estimates for porous silica materials with different surfaces based on different silica nanoparticles.)

[0053] Figure 8 The SSA estimates for products 1a-1j are shown. The SSA estimates involve using Formulas 2-4 with varying apparent nanoparticle sizes. This method assumes a single nanoparticle feed for forming the porous layer.

[0054] Figure 9 FIB / SEM images of products 1j and 2r are shown.

[0055] Figure 10 The pore size distributions of products 3a, 7a, and 7b obtained from nitrogen adsorption measurements (desorption, dV / dLog(D)) are shown.

[0056] Figure 11 The pore size distributions of products 3c, 7c, and 7d obtained from nitrogen adsorption measurements (desorption, dV / dLog(D)) are shown.

[0057] Figure 12 The pore size distributions of products 3e, 7e, and 7f obtained from nitrogen adsorption measurements (desorption, dV / dLog(D)) are shown.

[0058] Figure 13 FIB / SEM images of products 3e and 7f are shown.

[0059] Figure 14 The pore size distributions of products 1j, 3a, and 3f obtained from nitrogen adsorption measurements (desorption, dV / dLog(D)) are shown.

[0060] Figure 15 FIB / SEM images of products 3f, 7g, and 7h are shown.

[0061] Figure 16The table shows the estimated surface area and pore size distribution in the porous layer from the core surface (normalized distance = 0) to the outer particle surface (normalized distance = 1) for product 3a. These estimates do not include pore characteristic bias near 0.

[0062] Figure 17 The table shows the estimated surface area and pore size distribution in the porous layer from the core surface (normalized distance = 0) to the outer particle surface (normalized distance = 1) for product 3e. These estimates do not include pore characteristic bias near 0.

[0063] Figure 18 The table shows the estimated porous layer surface area (SA) from the core particle (normalized distance = 0) to the particle surface (normalized distance = 1) for products 5a-5c. These estimates do not include pore characteristic bias near 0.

[0064] Figure 19 The table shows the estimated pore size (PD) of the porous layer from the core particle (normalized distance = 0) to the particle surface (normalized distance = 1) for products 5a-5c. These estimates do not include pore characteristic bias near 0.

[0065] Figure 20 The diagram shows the estimated pore size (PD) of the porous layer from the core surface (x-axis origin) to the outer surface (x-axis rightmost point) for the product of Example 6. With Rho=0, the x-axis origin represents the center of the fully porous material. These estimates do not include pore characteristic deviations near 0.

[0066] Figure 21 The table shows the estimated surface area and pore size distribution in the porous layer from the core surface (normalized distance = 0) to the outer particle surface (normalized distance = 1) for product 7e. These estimates do not include pore characteristic bias near 0.

[0067] Figure 22 The table shows the estimated surface area and pore size distribution in the porous layer from the core surface (normalized distance = 0) to the outer particle surface (normalized distance = 1) for product 7f. These estimates do not include pore characteristic bias near 0.

[0068] Figure 23 An optional model is shown for estimating the surface area and pore size distribution in the porous layer from the core surface (normalized distance = 0) to the outer particle surface (normalized distance = 1) for product 7f. These estimates do not include pore characteristic biases near 0.

[0069] Figure 24 Table 6 shows the molecular weight and approximate molecular radius of the selected proteins under the reported molecular size fitting models 1-4.

[0070] Figure 25The cross-sectional geometry of porous and fully porous particles on the surface of the dual-porosity region is shown, where c = particle center; d = core diameter; d' = particle diameter; l = particle radius; Figure 26 The cross-sectional geometry of the porous particles on the annular or ring-shaped surface is shown, where d1 = diameter of the ring spanning the material; d2 = diameter of the non-porous core ring spanning the material; d3 = diameter of the internal empty ring; d4 = diameter of the cross-sectional particle; c1 = center of the material ring (see d1 / 2); 11 = radius from the center of the material ring to the surface of the material ring; 0 = pore start along the radius; 1 = porous layer end along the radius.

[0071] Figure 27 It is a graphical representation of Ostwald's work.

[0072] Figure 28 This describes a synthesis scheme that can be used to prepare the materials of this invention. The scheme is described in detail below. Detailed Implementation

[0073] This invention provides, for example, novel chromatographic materials for chromatographic separation, methods for their preparation, and separation apparatus comprising the chromatographic materials. The invention is described more fully with reference to the definitions listed below.

[0074] definition This invention provides, for example, novel chromatographic materials for chromatographic separation, methods for their preparation, and separation apparatus comprising the chromatographic materials. The invention is described more fully with reference to the definitions listed below.

[0075] "Hybrids" (including "hybrid inorganic / organic materials") include inorganic-based structures in which organic functional groups are integrally integrated with the internal or "skeleton" inorganic structure and the surface of the hybrid material. The inorganic portion of the hybrid material may be, for example, alumina, silicon dioxide, titanium, cerium, or a ceramic material; in an advantageous embodiment, the inorganic portion of the hybrid material is silicon dioxide. Exemplary hybrid materials are shown above in U.S. Patents 4,017,528, 6,528,167, 6,686,035, and 7,175,913 and International Application Publication WO2008 / 103423.

[0076] The term "alicyclic group" includes a closed ring structure with three or more carbon atoms. Alicyclic groups include cycloalkanes or cycloalkanes (i.e., saturated cycloalkanes), unsaturated cycloalkenes with two or more double bonds, and cycloalkynes with one triple bond. They do not include aromatic groups. Examples of cycloalkanes include cyclopropane, cyclohexane, and cyclopentane. Examples of cycloalkenes include cyclopentadiene and cyclooctatetraene. Alicyclic groups also include fused-ring structures and substituted alicyclic groups, such as alkyl-substituted alicyclic groups. In examples of alicyclic groups, such substituents may also include lower alkyl, lower alkenyl, lower alkoxy, lower alkylthio, lower alkylamino, lower alkylcarboxyl, nitro, hydroxyl, -CF3, -CN, etc.

[0077] The term "aliphatic group" includes organic compounds typically having 1 to 22 carbon atoms and characterized by straight or branched chains. Aliphatic groups include alkyl groups, alkenyl groups, and alkynyl groups. In complex structures, the chain may be branched or cross-linked. Alkyl groups include saturated hydrocarbons having one or more carbon atoms, including straight-chain alkyl and branched alkyl groups. Such hydrocarbon moieties may be substituted on one or more carbons by, for example, halogen, hydroxyl, thiol, amino, alkoxy, alkylcarboxyl, alkylthio, or nitro groups. Unless the number of carbons is otherwise specified, as used herein, "lower aliphatic" means an aliphatic group as defined above (e.g., lower alkyl, lower alkenyl, lower alkynyl) but having one to six carbon atoms. Representative examples of such lower aliphatic groups include lower alkyl groups such as methyl, ethyl, n-propyl, isopropyl, 2-chloropropyl, n-butyl, sec-butyl, 2-aminobutyl, isobutyl, tert-butyl, 3-thiopentyl, etc. As used herein, the term "nitro" means -NO2; the term "halogen" means -F, -Cl, -Br, or -I; the term "thiol" means SH; and the term "hydroxyl" means -OH. Therefore, as used herein, the term "alkylamino" means an alkyl group as defined herein, having an amino group attached thereto. Suitable alkylamino groups include groups having 1 to about 12 carbon atoms, advantageously 1 to about 6 carbon atoms. The term "alkathio" refers to an alkyl group as defined herein, having a mercapto group attached thereto. Suitable alkathio groups include groups having 1 to about 12 carbon atoms, advantageously 1 to about 6 carbon atoms. As used herein, the term "alkylcarboxyl" means an alkyl group as defined herein, having a carboxyl group attached thereto. As used herein, the term "alkoxy" means an alkyl group as defined herein, having an oxygen atom attached thereto. Representative alkoxy groups include those having 1 to 12 carbon atoms, advantageously 1 to 6 carbon atoms, such as methoxy, ethoxy, propoxy, tert-butoxy, etc. The terms "alkenyl" and "alkynyl" refer to unsaturated aliphatic groups similar to alkyl groups, but each containing at least one double or triple bond. Suitable alkenyl and alkynyl groups include those having 2 to 12 carbon atoms, advantageously 1 to 6 carbon atoms.

[0078] The term "alkyl" includes saturated aliphatic groups, including straight-chain alkyl groups, branched alkyl groups, cycloalkyl (alicyclic) groups, alkyl-substituted cycloalkyl groups, and cycloalkyl-substituted alkyl groups. In some embodiments, the straight-chain or branched alkyl group has 30 or fewer carbon atoms in its main chain, for example, C1-C30 for the straight chain or C3-C30 for the branched chain. In some embodiments, the straight-chain or branched alkyl group has 20 or fewer carbon atoms in its main chain, for example, C1-C20 for the straight chain or C3-C20 for the branched chain, and more advantageously 18 or fewer carbon atoms. Similarly, advantageous cycloalkyl groups have 4 to 10 carbon atoms in their ring structure, and more advantageously 4 to 7 carbon atoms in the ring structure. The term "lower alkyl" refers to an alkyl group having 1 to 6 carbon atoms in its chain, and to a cycloalkyl group having 3 to 6 carbon atoms in its ring structure.

[0079] Furthermore, as used throughout the specification and claims, the term "alkyl" (including "lower alkyl") includes both "unsubstituted alkyl" and "substituted alkyl," the latter referring to an alkyl moiety having substituents replacing hydrogen on one or more carbons in the hydrocarbon backbone. Such substituents may include, for example, halogens, hydroxyl groups, alkyl carbonyloxy groups, aryl carbonyloxy groups, alkoxy carbonyloxy groups, aryloxy carbonyloxy groups, carboxylic acid ester groups, alkyl carbonyl groups, alkoxy carbonyl groups, amino carbonyl groups, alkyl thiocarbonyl groups, alkoxy groups, phosphate ester groups, phosphonic acid groups, phosphonite groups, cyano groups, amino groups (including alkylamino, dialkylamino, arylamino, diarylamino, and alkylarylamino), amide groups (including alkyl carbonylamino, aryl carbonylamino, carbamoyl, and urea), amido groups, imino groups, hydrogen thioyl groups, alkyl thioyl groups, aryl thioyl groups, thiocarboxylic acid ester groups, sulfate ester groups, sulfonate groups, aminosulfonyl groups, sulfinylamino groups, nitro groups, trifluoromethyl groups, cyano groups, azide groups, heterocyclic groups, aralkyl groups, or aromatic or heteroaromatic moieties. Those skilled in the art will understand that, where appropriate, the substituted portion of the hydrocarbon chain may be substituted itself. Cycloalkyl groups may be further substituted, for example, by the substituents described above. The “aryl” moiety is an alkyl group that is substituted with an aryl group having, for example, 1 to 3 independent or fused rings and 6 to 18 carbon ring atoms, such as phenylmethyl (benzyl).

[0080] As used herein, the term "amino" refers to an unsubstituted or substituted moiety of the formula -NRaRb, wherein Ra and Rb are each independently hydrogen, alkyl, aryl, or heterocyclic, or Ra and Rb together with the nitrogen atom to which they are attached form a cyclic moiety having 3 to 8 ring atoms. Therefore, unless otherwise indicated, the term "amino" includes cyclic amino moietyes such as piperidinyl or pyrrolidinyl groups. "Amino-substituted amino group" refers to an amino group in which at least one of Ra and Rb is further substituted with an amino group.

[0081] The term "aromatic group" includes unsaturated cyclic hydrocarbons comprising one or more rings. Aromatic groups include 5- and 6-membered monocyclic groups that may contain zero to four heteroatoms, such as benzene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine. The aromatic ring may be substituted at one or more ring positions with, for example, halogens, lower alkyl groups, lower alkenyl groups, lower alkoxy groups, lower alkylthio groups, lower alkylamino groups, lower alkylcarboxyl groups, nitro groups, hydroxyl groups, -CF3, -CN, etc.

[0082] The term "aryl" includes 5- and 6-membered monocyclic aromatic groups that may contain zero to four heteroatoms, such as unsubstituted or substituted benzene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine, and pyrimidine. Aryl groups also include polycyclic fused aromatic groups, such as naphthyl, quinolinyl, and indolyl. The aromatic ring may be substituted at one or more ring positions with such substituents, for example, those described above for alkyl groups. Suitable aryl groups include unsubstituted and substituted phenyl groups. As used herein, the term "aryloxy" means an aryl group as defined herein that has an oxygen atom attached thereto. As used herein, the term "arylalkoxy" means an aryl alkyl group as defined herein that has an oxygen atom attached thereto. Suitable arylalkoxy groups have 1 to 3 free or fused rings and 6 to 18 carbocyclic atoms, such as O-benzyl.

[0083] The term "ceramic precursor" is intended to include any compound that leads to the formation of ceramic materials.

[0084] The term "chiral moiety" is intended to include any functional group that allows for chiral or stereoselective synthesis. Chiral moiety includes, but is not limited to, substituent groups having at least one chiral center, natural and non-natural amino acids, peptides and proteins, derived cellulose, macrocyclic antibiotics, cyclodextrins, crown ethers, and metal complexes.

[0085] The term "chromatographically enhanced pore geometry" refers to the pore structure geometry of the currently disclosed materials, which has been found to enhance the chromatographic separation capabilities of the materials, for example, as distinguishing them from other chromatographic media in the art. For example, geometric features can be formed, selected, or constructed, and various properties and / or factors can be used to determine whether the chromatographic separation capabilities of the material are "enhanced," for example, compared to geometric features known or conventionally used in the art. Examples of these factors include higher separation efficiency, longer column lifetime, and higher mass transfer characteristics (as evidenced by, for example, reduced band broadening and good peak shape). These properties can be measured or observed using techniques recognized in the art. For example, the chromatographically enhanced pore geometry of the porous materials of the present invention differs from prior art particles in that it lacks "ink bottle" or "shell-shaped" pore geometry or morphology, both of which are undesirable because they, for example, reduce mass transfer rates, resulting in lower efficiency. Chromatographically enhanced pore geometry exists in porous materials containing only small populations of micropores. Porous materials with such low micropore surface area (MSA) provide chromatographic enhancements, including high separation efficiency and good mass transfer properties (as evidenced by, for example, reduced band broadening and good peak shape). Micropore surface area (MSA) is defined as the surface area of ​​pores with a diameter less than or equal to 34 Å, and is determined using the BJH method by multipoint nitrogen adsorption analysis via adsorption isotherms log. As used herein, the abbreviations “MSA” and “MPA” are used interchangeably to refer to “micropore surface area”.

[0086] The term "functionalized group" includes organic functional groups that impart specific chromatographic functions to the chromatographic stationary phase.

[0087] The term "heterocyclic group" includes closed-ring structures in which one or more ring atoms are elements other than carbon, such as nitrogen, sulfur, or oxygen. Heterocyclic groups can be saturated or unsaturated, and heterocyclic groups such as pyrrole and furan can have aromatic characteristics. They include fused-ring structures such as quinoline and isoquinoline. Other examples of heterocyclic groups include pyridine and purine. Heterocyclic groups may also be substituted at one or more constituent atoms with, for example, halogens, lower alkyl groups, lower alkenyl groups, lower alkoxy groups, lower alkylthio groups, lower alkylamino groups, lower alkylcarboxyl groups, nitro groups, hydroxyl groups, -CF3, -CM, etc. Suitable heteroaromatic and heterocyclic groups typically have 1 to 3 independent or fused rings containing 3 to 8 members / rings and one or more N, O or S atoms, such as coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidinyl, furanyl, pyrroleyl, thiophenyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuran, tetrahydropyran, piperidinyl, morpholino, and pyrroleyl.

[0088] The term "metal oxide precursor" is intended to include any compound containing a metal that results in the formation of a metal oxide such as aluminum oxide, silicon dioxide, titanium dioxide, zirconium oxide, or cerium oxide.

[0089] The term "monolithic" is intended to encompass an assembly of individual particles packed into a bed form, wherein the shape and morphology of the individual particles are maintained. The particles are advantageously packed using a material that binds the particles together. A variety of binders known in the art can be used, for example, such as linear or cross-linked polymers of divinylbenzene, methacrylates, polyurethanes, olefins, alkynes, amines, amides, isocyanates, or epoxy groups, as well as condensation reactants of organoalkoxysilanes, tetraalkoxysilanes, polyorganoalkoxysiloxanes, polyethoxysiloxanes, and ceramic precursors. In some embodiments, the term "monolithic material" also includes hybrid monolithic materials prepared by other methods, such as those detailed in U.S. Patent 7,250,214; hybrid monolithic materials prepared by condensation of one or more monomers comprising 0 mol% to 99 mol% silica (e.g., SiO2); hybrid monolithic materials prepared from aggregated porous inorganic / organic particles; hybrid monolithic materials with chromatographically enhanced pore geometry; hybrid monolithic materials with chromatographically non-enhancing pore geometry; hybrid monolithic materials with ordered pore structures; hybrid monolithic materials with aperiodic pore structures; hybrid monolithic materials with amorphous or non-crystalline molecular order; hybrid monolithic materials with crystalline regions or crystalline zones; hybrid monolithic materials with various macropore and mesopore characteristics; and hybrid monolithic materials with various aspect ratios. In some embodiments, the term "monolithic material" also includes inorganic monolithic materials, such as those from G. Guiochon / J. Chromatogr. A Those described in 1168 (2007) 101-168.

[0090] The term "nanoparticle" refers to a microscopic member of a microscopic particle / abrasive or powder / nanopowder that can be crystalline or amorphous, and has at least one size smaller than about 100 nm, for example, a diameter or particle thickness smaller than about 100 nm (0.1 nm). Nanoparticles possess properties that differ from and are generally superior to conventional bulk materials, including, for example, greater strength, hardness, ductility, sinterability, and greater activity. Extensive scientific research continues to determine the properties of nanomaterials, and a small number of nanomaterials have been synthesized (primarily as nanoscale powders) through various methods, including colloidal precipitation, mechanical milling, and vapor-phase nucleation and growth. Extensive reviews document recent developments in nanophase materials and are incorporated herein by reference: Gleiter, H. (1989) "Nano-crystalline materials," Prog. Mater. Sci. 33:223-315 and Siegel, R, W. (1993) "Synthesis and properties of nano-phase materials," Mater. Sci. Eng. A168:189-197. In some embodiments, the nanoparticles comprise oxides or nitrides of silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, and mixtures thereof. In some embodiments, the nanoparticles of the present invention are selected from diamond, zirconium oxide (amorphous, monoclinic, tetragonal, and cubic), titanium dioxide (amorphous, anatase, brookite, and rutile forms), aluminum (amorphous, α, and γ forms), and boron nitride (cubic form). In particular embodiments, the nanoparticles of the present invention are selected from nanodiamond, silicon carbide, titanium dioxide (anatase form), cubic boron nitride, and any combination thereof. Furthermore, in particular embodiments, the nanoparticles may be crystalline or amorphous. In particular embodiments, the nanoparticles have a diameter less than or equal to 100 nm, for example, less than or equal to 50 nm, for example, less than or equal to 20 nm.

[0091] Furthermore, it should be understood that nanoparticles characterized by dispersion within the composites of the present invention are intended to describe exogenously added nanoparticles. This differs from nanoparticles capable of in-situ formation, or formations that are significantly similar to presumed nanoparticles, wherein, for example, macromolecular structures such as particles may contain aggregates of these formed endogenously.

[0092] The term “substantially disordered” refers to the lack of pore order based on X-ray powder diffraction analysis. Specifically, “substantially disordered” is defined by the absence of peaks at diffraction angles in the X-ray diffraction pattern corresponding to a d-value (or d-spacing) of at least 1 nm.

[0093] "Surface modifiers" include (typically) organic functional groups that impart specific chromatographic functions to the chromatographic stationary phase. Porous inorganic / organic hybrid particles have both organic groups and silanol groups that can be additionally replaced or derivatized by surface modifiers.

[0094] The term "surface modification" is used herein to describe composite materials of the present invention having both organic groups and silanol groups that can be further substituted or derivatized by a surface modifier. A "surface modifier" includes organic functional groups that (typically) impart specific chromatographic functionality to a chromatographic stationary phase. Surface modifiers, as disclosed herein, are attached to a substrate material, for example, via derivatization or coating followed by crosslinking, thereby imparting the chemical characteristics of the surface modifier to the substrate material. In one embodiment, the organic groups of a hybrid material, such as particles, react with the surface modifier to form organic covalent bonds. The modifier can form organic covalent bonds with the organic groups of the material via a variety of mechanisms known in the fields of organic and polymer chemistry, including but not limited to nucleophilic, electrophilic, cycloaddition, radical, carbene, nitrobenzene, and carbocation reactions. An organic covalent bond is defined as a covalent bond formed between common elements of organic chemistry, including but not limited to hydrogen, boron, carbon, nitrogen, oxygen, silicon, phosphorus, sulfur, and halogens. Furthermore, carbon-silicon and carbon-oxygen-silicon bonds are defined as organic covalent bonds, while silicon-oxygen-silicon bonds are not defined as organic covalent bonds. Various synthetic transformants are well known in the literature; see, for example... March, J. Advanced Organic Chemistry , No. 3 version, Wiley, New York, 1985 .

[0095] The terms "composite material" and "complex" are used interchangeably herein to describe the engineered materials of the present invention, which are composed of one or more components combined with dispersed nanoparticles, wherein each component / nanoparticle remains separated and isolated at a macroscopic level within the final structure. The composite materials of the present invention are form-independent and can be integral or particulate in nature. Furthermore, the simplified form of the convention can be used to describe composite materials containing dispersed nanoparticles, i.e., Np / (A). w (b) x (C) yAnd it can be understood as follows: the symbol to the left of the slash represents dispersed nanoparticles, and the symbol to the right of the slash represents a component of material in which nanoparticles (marked to the left of the slash) are dispersed. In some embodiments, the composite material of the present invention may be a nanocomposite material, which is known to include at least, for example, nano / nanotype, internal type, intermediate type, and internal / intermediate type. (Nanocomposites Science and Technology, edited by PMAjayan, LS Schadler, PV Braun, Wiley-VCH (Weinheim, Germany), 2003) The terms "material with high thermal conductivity," "high thermal conductivity core," and "high thermal conductivity additive" are defined as materials, core materials, or composite additives with a thermal conductivity greater than 20 W / (m·K). In various embodiments, the additive has a thermal conductivity in the following ranges: about 20 W / (m·K) to no more than 3500 W / (m·K); about 100 W / (m·K) to no more than 3300 W / (m·K); and 400 W / (m·K) to no more than 3000 W / (m·K). The high thermal conductivity core or additive may be, for example, but not limited to, core particles of 0.1 µm to 8 µm, nanoparticle additives, or metal oxide precursors. In various embodiments, the high thermal conductivity core or additive includes (but is not limited to) aluminum, copper, gold, and diamond.

[0096] A "high thermal diffusivity" core or additive is defined as one with a thermal diffusivity greater than 20 mm. 2 / s of additives used in surface porous materials. In various embodiments, the core or additive has a thermal diffusivity range of approximately 20 mm. 2 / s to no more than 2000mm 2 / s; approximately 100mm 2 / s to no more than 1600mm 2 / s; and 150mm 2 / s to no more than 1400mm 2 / s. The high thermal conductivity core or additive may be a core particle of 0.1µm to 8µm, a nanoparticle additive, or a metal oxide precursor. In various embodiments, the high thermal conductivity core or additive includes (but is not limited to) aluminum, copper, gold, and diamond.

[0097] "High thermal conductivity surface porous materials (or particles)" are defined as materials with improved thermal conductivity or thermal diffusivity compared to porous silica particles of the same size. In various embodiments, a surface porous material with higher thermal conductivity is a material whose thermal conductivity or thermal diffusivity is improved relative to surface porous silica particles of the same size. In various embodiments, a surface porous material with higher thermal conductivity is a material whose thermal conductivity is improved relative to fully porous hybrid particles of the same size. Considering the differences in bulk material properties, pore volume, type of surface modification, and coverage, this can be achieved through Gritti and Guiochon [J. Chromatogr. A, 2010, ...]. 1217 The particle thermal conductivity was determined using the method described in 5137.

[0098] The terms "magnetic material," "magnetic core," and "magnetic additive" are defined as having a magnetic flux density greater than 15 emu / g (Am) at room temperature. 2 Materials, core materials, or composite additives with a magnetic susceptibility (σ, magnetic moment per unit mass, magnetic saturation or saturation magnetization) of ( / kg). This includes ferromagnetic and ferrimagnetic materials, including (but not limited to): magnetite (magnetic iron oxide); hematite; yttrium iron garnet, cobalt, CrO2; and ferrites containing iron and Al, Mg, Ni, Zn, Mn, or Co. Magnetic core particles do not include other iron oxides, including hematite and goethite with magnetic susceptibility values ​​less than 10 emu / g. Hematite (0.4 emu / g) is considered antiferromagnetic at room temperature.

[0099] As used herein, the term "fine particles" refers to undesirable material produced in the methods of this invention that is less than 10% by volume of the target particle size distribution. Fine particles can be formed by recrystallization events or particle breakage. The resulting fine particles can be non-porous or fully porous. Typically, fine particles are substantially less than 10% by volume of the target particle size distribution. Typically, the size of fine particles is <1 μm. Chromatographic problems caused by extremely small fine particles include percolation through the packed bed and blockage in the outlet glass frit. This results in increased column pressure. Alternatively, fine particles small enough to percolate through the packed bed and outlet glass frit can cause detector problems and can contaminate the product. Detector problems include blocked flow channels, obstructed detector windows, and abnormal detector readouts. Such problems can shorten detector life and may require extensive cleaning protocols. Such problems can also affect the precision, accuracy, reliability, repeatability, and robustness of the generated analytical data. Fine particles can be removed by fractionation.

[0100] As used herein, the terms "aggregate" and "absorptive" refer to undesirable materials generated in the methods of this invention with a particle size distribution greater than 90% by volume of the target size. Aggregates and / or agglomerates can form due to core material defects, inappropriate mixing or dispersion in the method, or excessive forces during post-processing. Aggregates and agglomerates can affect the efficiency, permeability, repeatability, and robustness of the packed bed within the column. It is difficult to optimally pack the column with materials that have increased amounts of aggregates and agglomerates. Aggregates and agglomerates can break up within the packed bed structure when exposed to high pressures and shears. This can lead to mechanical instability of the packed bed and resulting voids at the column top. The breakup of these aggregates and agglomerates can also lead to the generation of fine particles. Aggregates and agglomerates can be removed by fractionation.

[0101] As used herein, the term "substantially nonporous" refers to a material that, while porous, is impermeable or otherwise acts as a nonporous material. Such substantially nonporous materials have a pore volume of less than about 0.10 cc / g.

[0102] As used herein, the term "controlled porosity" refers to porosity that develops into a predetermined or desired shape or pattern. In some cases, controlled porosity refers to variations in an established porous surface, such as the addition of narrower pore sizes to create a wider pore network. In other cases, controlled porosity refers to porosity that develops into a specific pattern, as measured from the core material to the outermost surface.

[0103] As used herein, the term "surface" refers to the structure of the outermost portion of a material, core, or layer. Therefore, the master surface refers to the structure of the chromatographic core material before any surface layers are added. Similarly, the outermost surface refers to the outermost portion of the final material after all layers have been completed.

[0104] As used herein, the term "90 / 10 ratio" refers to the ratio of the particle size distribution of the particulate material of the present invention. In the 90 / 10 ratio, the particle size of the material is measured and plotted as an S-curve. The particle size value represented by 90% of the particles (i.e., 90% of the particles are equal to or smaller than this value) is compared to the particle size value represented by 10% of the particles (i.e., 10% of the particles are equal to or smaller than this value).

[0105] Ostwald ripening and controlled porosity The material of this invention employs Ostwald ripening in the construction of sol-based structures with isotropic or anisotropic macroporosity gradients. The net effect of Ostwald ripening is described in... Figure 27 middle.

[0106] By utilizing this effect, nanoparticles and / or smaller sols with higher surface areas and positive curvature preferentially dissolve and deposit into regions with lower or negative curvature. An advantage of this invention is its ability to create unique porosity in pre-formed surfaces. Specifically, the preferential treatment of smaller nanoparticles and sols relative to larger nanoparticles and sols allows for the creation of predetermined pore patterns regarding pore shape, pore size, pore volume, or specific surface area. For example, if the pre-formed surface is a membrane (e.g., 0.2 pm polypropylene or 0.2 pm anodized aluminum oxide), unique pores with high-to-low, low-to-high pore size variations, repeating porosity characteristics, or any of these possibilities can be prepared to create unique porous devices suitable for sample preparation, sample concentration, solvent purification, ultracentrifugation membranes, dialysis membranes, salt bridges, or other applications.

[0107] If the preformed surface is a fully porous particle, this method can be used to produce new fully porous particles with unique properties. For example, the preformed fully porous particles may have pore sizes advantageous for some applications (i.e., 550 Å for desalination), while larger pores may be used for other applications (i.e., reverse-phase protein or peptide separation). The end result is a separation apparatus that performs more than one separation simultaneously or sequentially.

[0108] For example, when the pre-formed fully porous particles have a wide pore size (e.g., >1000 angstroms), this method can be used to create additional porosity within the same particle size. In this method, the wider pores act as a support for the internal pores.

[0109] This method can be used to increase the surface porosity of particles. This creates a difference in external membrane mass transfer and improves diffusion into the porous network. Such methods have practical applications in column separation and sample preparation equipment.

[0110] When the preformed surface is a fully porous particle, this method can be used to produce novel particle morphologies. Through variations of the method of this invention, spherical preformed particles can be modified to form non-spherical particles, elliptical particles, dumbbell-shaped particles, granular particles, or agglomerated materials. Such materials can be advantageously used in chromatography to produce novel column-packed materials with acceptable efficiency at lower column pressures. These controlled-morphology particles can offer the many benefits of bulk materials without the synthetic complexity, porosity, or reproducibility considerations of bulk materials.

[0111] Alternatively, when the preformed surface is a fully porous, non-spherical particle, this method can be used to produce more spherical or even highly spherical particles. Improved particle size distribution can also be achieved.

[0112] When the preformed surface is a monolithic material, this method can be used to produce new monolithic materials with unique properties. The use of an adaptive porous layer on the exterior of the preformed monolith allows for improved cladding or pillar fabrication. The use of an outer layer containing organic functional groups allows for improved, unique ways of wall attachment. The use of monolithic materials in this invention allows for improved porosity control. For example, open monolithic materials containing fewer mesopores and almost entirely macropores can benefit from this technology when acting as three-dimensional scaffolds forming mesopores or porous frameworks.

[0113] When the preformed surface is an open support (e.g., wire mesh, glass wool, fiber mesh), novel porous materials and devices with unique porosity can be formed. A particular aspect of the invention is the case where the preformed surface is a flexible tube or wire. New monolithic materials with flexible or annular structures can be prepared by layer-by-layer deposition using impregnation coating. Such materials can be used for micro-sampling, DBS-alternative schemes, and sample preparation for LC / MS and SPME equipment.

[0114] When the preformed surface is a capillary wall (e.g., a glass-walled capillary, alumina-surface microfluidic device, ceramic microfluidic device, titanium dioxide microfluidic device, plastic capillary, or microfluidic device), the present invention can be used to modify the wall structure (e.g., modifying a square channel to have rounded corners or a cross-section closer to a circle). Alternatively, the method can be controlled to produce new porous layer open tubes. One consideration for conventional methods of producing silica PLOT columns is the need to use elevated temperatures to remove polymeric electrolytes and other binding chemicals—and to sinter or mechanically strengthen the porous layer.

[0115] This invention allows for a unique method of generating hybrid materials through the redistribution of dissolved silicates. When using a mixture of hybrid sol and silica sol, the hybrid network is more resistant to alkali treatment, while the silica sol is more readily soluble. This can be used homogeneously or heterogeneously. In one aspect of the invention, we can create specific layers or regions within porous layers with increased hybrid or silica content.

[0116] In specific implementations, the present invention allows for a unique way of generating controlled porosity in surface porous materials.

[0117] Core and shell materials: The present invention provides porous materials, particles and / or bulk materials comprising one or more layers of a core and a chromatographic surface material surrounding the core.

[0118] In some embodiments, the porous material of the present invention exhibits a substantially narrow particle size distribution. In some other embodiments, the 90 / 10 ratio of particle size is 1.00-1.55. In specific embodiments, the 90 / 10 ratio of particle size is 1.00-1.10 or 1.05-1.10. In other specific embodiments, the 90 / 10 ratio of particle size is 1.10-1.55; 1.10-1.50; or 1.30-1.45.

[0119] In some embodiments of the porous material of the present invention, the material has pore geometry features that enhance chromatographic properties. That is, in some embodiments, the surface porous material of the present invention has only a small population of micropores.

[0120] In one embodiment, the porous material of the present invention does not have pore geometry features that enhance chromatography. In another embodiment, the HPCM of the present invention has pore geometry features that enhance chromatography.

[0121] In some embodiments, the porous material of the present invention has a porosity of about 25 μm. 2 / g to 1100m 2 / g; approximately 80m 2 / g to 500m 2 / g; or approximately 120m 2 / g to 330m 2 / g of surface area.

[0122] In other embodiments, the porous material of the present invention has a porous diameter of approximately 0.15 cm. 3 / g to 1.7cm 3 / g; or approximately 0.5cm 3 / g to 1.3cm 3 / g pore volume.

[0123] In some other embodiments, the porous material of the present invention is non-porous.

[0124] In other embodiments, the porous material of the present invention has a porous structure with a diameter of less than about 110 μm. 2 / g; less than approximately 105m 2 / g; less than approximately 80m 2 / g; or less than about 50m 2 / g microporous surface area.

[0125] In other embodiments, the porous material of the present invention has an average pore size of about 20 Å to 1500 Å; about 50 Å to 1000 Å; about 100 Å to 750 Å; or about 150 Å to 500 Å.

[0126] When measuring pore volume, surface area, pore diameter, etc., the measurement refers to the outermost surface of the chromatographic material.

[0127] In some embodiments of the invention, each layer of one or more chromatographic surface materials independently comprises one or more nanoparticles. In some embodiments, each of the one or more nanoparticles is independently an inorganic material or an inorganic / organic hybrid material.

[0128] In some implementations, the materials used in the various layers of the chromatographic surface material may be a mixture of more than one type of material.

[0129] In a particular embodiment, each of the one or more nanoparticles has an average diameter of 1 nm to 400 nm or 5 nm to 200 nm.

[0130] In some embodiments, each layer of one or more chromatographic surface materials independently comprises two or more types of nanoparticles with different average diameters. In a particular embodiment, each layer independently comprises nanoparticles with different average diameters, wherein the two different average diameters are a larger average diameter and a smaller average diameter. In a specific embodiment, the diameter ratio of nanoparticles with a larger average diameter to nanoparticles with a smaller average diameter in each layer is independently greater than 1.75; in the range of 1.75 to 100, or in the range of 2 to 50. In other specific embodiments, the weight ratio of nanoparticles with a larger average diameter to nanoparticles with a smaller average diameter in each layer is independently from about 19:1 to 0.05:1; from about 15:1 to about 0.25:1; or from about 10:1 to about 0.5:1.

[0131] As Rekeler (US 3709664) states, "The properties of the silica gel obtained, particularly the porosity characteristics, are discussed in terms of pore volume (PV), surface area (SA), and average pore diameter (PD), where PD = 4PV / SA. The determinations of these values ​​are made by nitrogen absorption-desorption techniques well known in the art and described in detail in the Journal of the American Chemical Society, Volume 60, Page 309 (1938), and the Journal of Catalysis, Volume 2, Page 111 (1955)." Catalysis,” Volume 2, Page 111 (1955)).

[0132] Therefore, it is well known in the art that particle porosity can be characterized using nitrogen adsorption analysis, specifically in terms of TPV, SSA, and APD. The correlation of physical properties, i.e., APD ~ 4TPV / SSA, follows a cylindrical pore model, which is best suited for materials with well-formed and open pore structures. This model does not precisely match closed or poorly formed pore structures. Nitrogen adsorption analysis works best for pores with an APD less than approximately 500 angstroms. This technique is well-suited for characterizing mesopores and micropores, but not for macroporous materials or materials containing large voids.

[0133] Core materials As discussed above, a core material is used to prepare the material of the present invention. The core material has a main surface that is subsequently modified by the chromatographic surface material to provide a chromatographic material having a predetermined pore size, shape, or composition.

[0134] In some embodiments, the core material is a non-porous core, a substantially non-porous core, a fully porous core, or a surface porous core. In most cases, a non-porous core or a substantially non-porous core is used. In specific embodiments, the core material is a solid material. That is, in some embodiments, the core material is not hollow.

[0135] In some embodiments, when using a non-porous or substantially non-porous core, the core material is silicon dioxide; silicon dioxide coated with an inorganic / organic hybrid surrounding material; magnetic core material; magnetic core material coated with silicon dioxide; high thermal conductivity core material; high thermal conductivity core material coated with silicon dioxide; composite material; inorganic / organic hybrid surrounding material; composite material coated with silicon dioxide; magnetic core material coated with an inorganic / organic hybrid surrounding material; or high thermal conductivity core material coated with an inorganic / organic hybrid surrounding material.

[0136] In some cases, the core material may be an inorganic / organic hybrid material. Similarly, in the above cases, the core may have a surrounding material made of an inorganic / organic hybrid material. In some embodiments, the inorganic / organic hybrid material has the formula: (SiO2) d / [R 2 ((R) p (R 1 ) q SiO t ) m (I) in, R and R 1 Each independently is C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18heterocycloalkyl, C5-C 18 aryl, C1-C 18 heteroaryl; or absent; wherein each R 2 is connected to two or more silicon atoms; p and q are each independently from 0.0 to 3.0, t is 0.5, 1.0, or 1.5; d is from 0 to about 30; m is an integer from 1 to 20; wherein R, R 1 and R 2 are optionally substituted; provided that: (1) when R 2 is absent, m = 1, and when 0 < p + q ≤ 3, ; and (2) when R 2 is present, m = 2 to 2, and when p + q ≤ 2, ; Formula: (SiO2) d / [(R) p (R 1 ) q SiO t (II) wherein, R and R 1 are each independently C1-C 18 alkoxy, C1-C 18 alkyl, C1-C 18 alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl, C3-C 18 cycloalkyl, C1-C 18 heterocycloalkyl, C5-C 18 aryl, C5-C 18 aryloxy, or C1-C<000​​​​​​​​​​​​​​​​​​​​​​​ R 1 For C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C1-C 18 heteroaryl; or nonexistent; where each R 2 Connected to two or more silicon atoms; d ranges from 0 to approximately 30; r can be 0, 1, or 2, provided that when r = 0, then t = 1.5; when r = 1, then t = 1; or when r = 2, then t = 0 or 5; and so on. m is an integer from 1 to 20; Mode: (A) x (B) y (C) z (IV) The repeating units A, B, and C can be arranged randomly, block, or a combination of random and block; A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit bonded to one or more repeating units B or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds; C is an inorganic repeating unit bonded to one or more repeating units B or C via inorganic bonds; x and y are positive numbers, and z is a non-negative number, where x + y + z = 1. In some embodiments, z = 0, then 0.002 ≤ x / y ≤ 210, and when z ≠ 0, then 0.0003 ≤ y / z ≤ 500 and 0.002 ≤ x / (y + z) ≤ 210; or Mode: (A) x (B) y (B*) y* (C) z (V) The repeating units A, B, B*, and C can be arranged randomly, block, or a combination of random and block; A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit bonded to one or more repeating units B or B* or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds; B* is an organosiloxane repeating unit bonded to one or more repeating units B or B* or C via inorganic siloxane bonds, wherein B* is an organosiloxane repeating unit that is a non-reactive (i.e., polymerizable) organic component and may further have protected functional groups that can be deprotected after polymerization; C is an inorganic repeating unit bonded to one or more repeating units B or B* or C via inorganic bonds; x and y are positive numbers, and z is a non-negative number, where x+y+z=1. In some implementations, when z=0, then 0.002≤x / (y+y*)≤210, and when z ≠ 0, then 0.0003≤(y+y*) / z≤500 and 0.002≤x / (y+y*+z)≤210.

[0137] When the core material is coated with an inorganic / organic hybrid surrounding material, the surrounding material can be porous, non-porous, or substantially non-porous, and the main surface of the core material is considered the outermost surface of the surrounding material.

[0138] In some embodiments, the core material is a composite material. A composite material describes an engineered material of the invention composed of one or more components described herein combined with dispersed nanoparticles, wherein each component / nanoparticle remains separated and isolated at a macroscopic level within the final structure. The composite materials of the invention are form-independent and can be integral or particulate in nature. Furthermore, this document uses the term Np / (A) to describe composite materials containing dispersed nanoparticles. w (b) x (C) yThe simplified form of the convention can be understood as follows: the symbol to the left of the slash indicates a dispersed nanoparticle, and the symbol to the right of the slash indicates a component of material in which nanoparticles (indicated to the left of the slash) are dispersed. In some embodiments, the composite material of the present invention may be a nanocomposite material, which is known to include at least, for example, nano / nanotype, internal type, intermediate type, and internal / intermediate type (Nanocomposites Science and Technology, edited by PM Ajayan, LS Sehadler, PV Braun, Wiley-VCH (Weinheim, Germany), 2003). The term "nanoparticle" is a microscopic member that may be crystalline or amorphous microparticles / abrasives or powders / nanopowders, and at least one size is less than about 100 nm, for example, a diameter or particle thickness of less than about 100 nm (0.1 µm).

[0139] Nanoparticles possess properties that differ from and are generally superior to conventional bulk materials, including, for example, greater strength, hardness, ductility, sinterability, and activity. Extensive scientific research continues to focus on determining the properties of nanomaterials, and a small number of nanomaterials have been synthesized (primarily as nanoscale powders) through various methods, including colloidal precipitation, mechanical milling, and vapor-phase nucleation and growth. Extensive reviews document the latest developments in nanophase materials and are incorporated herein by reference: Gleiter, H. (1989) “Nano-crystalline materials,” Prog. Mater. Sei. 33:223-315 and Siegel, RW (1993) “Synthesis and properties of nano-phase materials,” Mater. Sei. Eng. A168:189-197. In some embodiments, the nanoparticles comprise oxides or nitrides of silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, and mixtures thereof. In some embodiments, the nanoparticles of the present invention are selected from diamond, zirconium oxide (amorphous, monoclinic, tetragonal, and cubic), titanium dioxide (amorphous, anatase, brookite, and rutile forms), aluminum (amorphous, α, and γ forms), and boron nitride (cubic form). In specific embodiments, the nanoparticles of the present invention are selected from nanodiamond, silicon carbide, titanium dioxide (anatase form), cubic boron nitride, and any combination thereof. Furthermore, in specific embodiments, the nanoparticles may be crystalline or amorphous. In specific embodiments, the nanoparticles have a diameter less than or equal to 100 nm, for example, a diameter less than or equal to 50 nm, or for example, a diameter less than or equal to 20 nm.

[0140] Furthermore, it should be understood that nanoparticles characterized by dispersion within the composites of the present invention are intended to describe exogenously added nanoparticles. This differs from nanoparticles capable of in-situ formation, or formations that are significantly similar to presumed nanoparticles, wherein, for example, macromolecular structures such as particles may contain aggregates of these formed endogenously.

[0141] Nanoparticles are of great scientific interest because they can serve as effective bridges between bulk materials and atomic or molecular structures. Bulk materials should possess constant physical properties, independent of size, but this is not always the case at the nanoscale. Size-dependent properties have been observed, such as quantum confinement in semiconductor particles, surface plasmon resonances in some metal particles, and superparamagnetism in magnetic materials.

[0142] In some embodiments, the composite material includes a magnetic material, a material with high thermal conductivity, or a mixture thereof. Similarly, in some embodiments, the core itself is a magnetic material, a material with high thermal conductivity, or a mixture thereof.

[0143] Materials, high thermal conductivity cores, or high thermal conductivity additives are defined as materials with a thermal conductivity greater than 20 W / (m·K). In various embodiments, the additive has a thermal conductivity in the following ranges: about 20 W / (m·K) to no more than 3500 W / (m·K); about 100 W / (m·K) to no more than 3300 W / (m·K); and 400 W / (m·K) to no more than 3000 W / (m·K). The high thermal conductivity additive may be a core particle of 0.1 µm to 8 µm, a nanoparticle additive, or a metal oxide precursor. In various embodiments, the high thermal conductivity additive includes (but is not limited to) aluminum, copper, gold, and diamond.

[0144] High thermal diffusivity additives are defined as those with a thermal diffusivity greater than 20 mm. 2 The additive used in the surface porous particles of / s. In various embodiments, the additive has a thermal diffusivity range of approximately 20 mm. 2 / s to no more than 2000mm 2 / s; approximately 100mm 2 / s to no more than 1600mm 2 / s; and 150mm 2 / s to no more than 1400mm 2 / s. The high thermal conductivity additive can be a core particle from 0.1µm to 8µm, a nanoparticle additive, or a metal oxide precursor. In various embodiments, the high thermal conductivity additive includes (but is not limited to) aluminum, copper, gold, and diamond.

[0145] Magnetic materials include those with a strength greater than 15 emu / g (A m) at room temperature. 2 Materials with a magnetic susceptibility (σ, magnetic moment per unit mass, magnetic saturation or saturation magnetization) of 1 / kg. This includes ferromagnetic and ferrimagnetic materials, including (but not limited to): magnetite (magnetic iron oxide); hematite; yttrium iron garnet, cobalt, CrO2; and ferrites containing iron and Al, Mg, Ni, Zn, Mn or Co. Magnetic core particles do not include other iron oxides, including hematite and goethite with magnetic susceptibility values ​​less than 10 emu / g. Hematite (0.4 emu / g) is considered antiferromagnetic at room temperature.

[0146] In one embodiment, the core is spherical. In another embodiment, the spherical core has an amorphous or non-morphic molecular order. In yet another embodiment, the spherical core has a non-periodic porous structure.

[0147] In another embodiment, the core has an average size of about 0.1 µm to about 300 µm. In another embodiment, the core has an average size of about 0.1 µm to about 30 µm. In another embodiment, the core has an average size of about 0.5 µm to about 30 µm. In another embodiment, the core has an average size of about 0.9 µm to about 10 µm. In another embodiment, the core has an average size of about 1.0 µm to about 3.0 µm.

[0148] In some embodiments, the core material of the present invention has a substantially narrow particle size distribution. In some other embodiments, the particle size... 90 / 10 The ratio is 1.00-1.55. In specific implementation schemes, the particle size... 90 / 10 The ratio is 1.00-1.10 or 1.05-1.10. In other specific embodiments, the particle size... 90 / 10 The ratio is 1.10-1.55; 1.10-1.50; or 1.30-1.45.

[0149] In some embodiments, the core is hydrolyzed stable at a pH of about 1 to about 14. In one embodiment, the core is hydrolyzed stable at a pH of about 10 to about 14. In another embodiment, the core is hydrolyzed stable at a pH of about 1 to about 5.

[0150] Synthesis of core materials In one aspect, the core material can be any commercially available core material. In other embodiments, the core material can be synthesized using standard methods. In certain cases, specific methods can be used to prepare non-porous or substantially non-porous spherical, substantially spherical, or highly spherical core materials.

[0151] In one method, spherical silica or hybrid non-porous cores are prepared according to a standard protocol. The surface porous layer is formed using two or more of the following: TEOS, thermally degradable organofunctional silanes (e.g., acetoxypropyltrialkoxysilane or bromoethyltrialkoxysilane), along with more thermally stable hybrid silanes, such as (but not limited to) phenylene-bridged silanes. In this method, a low-temperature heat treatment (<500°C) is performed to degrade the thermally degradable organofunctional silane in a way that introduces porosity, while maintaining the more thermally stable hybrid groups. The temperature is determined by a TGA experiment performed in air. Additional steps of fractionation, pore modification, acid treatment, and bonding are performed, as detailed herein.

[0152] In another method, the spherical hybrid non-porous core is prepared according to a standard protocol. The porous surface layer is prepared using one or more silanes, including (but not limited to) TEOS, low-temperature degradable organofunctional silanes (e.g., acetoxypropyltrialkoxysilane or bromoethyltrialkoxysilane), ethylene-bridged alkoxysilanes, or phenylene-bridged alkoxysilanes, employing a method with one or more surfactants. The surfactant is removed using an acid-ethanol method (e.g., ethanol containing hydrochloric acid). Alternatively, when removing the surfactant, it is removed by heat treatment (<500°C) at a temperature that retains the hybrid groups. This temperature is determined by a TGA experiment performed in air. Alternatively, the surfactant is removed by oxidation (e.g., ozone decomposition). Alternatively, one or more surfactants used in this method are selected from acid-insecure, base-insecure, or other unstable surfactants. These unstable surfactants can react and are subsequently removed by selecting appropriate chemicals and conditions (e.g., acid hydrolysis, base hydrolysis, reduction or oxidation, hydrogenation or hydrogenolysis). As detailed above, additional steps such as grading, pore modification, acid treatment, and bonding are performed.

[0153] In another method, spherical silica or hybrid non-porous cores are prepared according to standard protocols. Hybrid sol (<100 nm) solutions are prepared individually using one or more silanes, including (but not limited to) TEOS, low-temperature degradable organic functional silanes (e.g., acetoxypropyltrialkoxysilane or bromoethyltrialkoxysilane), ethylene-bridged alkoxysilanes, or phenylene-bridged alkoxysilanes. A uniform surface porous layer is then prepared using a suitable positively charged polymeric electrolyte in a layer-by-layer manner. Suitable polymeric electrolytes include (but are not limited to) straight-chain, branched, and block polymers containing one or more of the following groups: alkyl, cycloalkyl, aryl, ethylene oxide groups, along with one or more of the following groups: primary, secondary, tertiary, and quaternary amino groups, pyrrolidones, pyridines, and imidazoles. When removing the polymeric electrolyte, it is removed by heat treatment (<500 °C) at a temperature that retains the hybrid groups. This temperature is determined by a TGA experiment performed in air. Alternatively, polymeric electrolytes are removed by ozone decomposition. Additional steps, including fractionation, pore modification, acid treatment, and bonding, are performed as detailed herein.

[0154] Chromatographic surface materials The material of the present invention has one or more chromatographic surface material layers applied to the core material. In some embodiments, one or more chromatographic surface materials are porous inorganic / organic hybrid materials; porous silica or porous composite materials.

[0155] In some aspects, the material of the present invention has a rough surface. In other aspects, the material of the present invention has a smooth surface. As used herein, In some implementations, the thickness of each porous layer is independently 0.02µm to 5µm, as measured perpendicular to the surface without a porous core.

[0156] In other embodiments, the thickness of each porous layer is independently 0.06µm to 1µm, as measured perpendicular to the surface without a porous core.

[0157] In other embodiments, the thickness of each porous layer is independently 0.20 µm to 0.70 µm, as measured perpendicular to the surface without a porous core.

[0158] In some embodiments, the material of the present invention has 1 to 30 layers of chromatographic surface material. In other embodiments, there are 2 to 5 layers of chromatographic surface material. In still other embodiments, there are 1 or 2 layers of chromatographic surface material.

[0159] In some implementations, the composition of each layer of the chromatographic shell material is selected independently.

[0160] In some embodiments, each layer of the chromatographic shell material independently has pores with an average diameter of about 20 Å to 1500 Å; about 25 Å to 600 Å; about 60 Å to 350 Å; about 80 Å to 300 Å; or about 90 Å to 150 Å.

[0161] In other embodiments, each layer of the chromatographic shell material independently has a thickness of approximately 0.1 cm. 3 / g to 1.50cm 3 / g; approximately 0.11cm 3 / g to 0.50cm 3 / g; approximately 0.09cm 3 / g to 0.45cm 3 / g; or approximately 0.17cm 3 / g to 0.30cm 3 / g average pore volume.

[0162] In other embodiments, each layer of the chromatographic shell material independently has approximately 10 μm. 2 / g to 1100m 2 / g; approximately 10m 2 / g to 400m 2 / g; approximately 15m 2 / g to 300m 2 / g; or approximately 60m 2 / g to 200m 2 / g of pore surface area.

[0163] Hybrid chromatographic surface materials In some implementations, the chromatographic surface material that can be layered onto the core can be derived independently from: One or more polymeric organic functional metal precursors and / or polymeric metal oxide precursors are condensed on the surface of the core, or A partially condensed polymeric organofunctional metal precursor, a mixture of two or more polymeric organofunctional metal precursors, or a mixture of one or more polymeric organofunctional metal precursors and a polymeric metal oxide precursor is applied to the surface of the core.

[0164] In some respects, the inorganic portion of the hybrid material is independently selected from alumina, silicon dioxide, titanium dioxide, cerium oxide, or zirconium oxide, as well as ceramic materials.

[0165] Alternatively, hybrid materials can be derived independently from: Condensation of one or more organofunctional silanes and / or tetraalkoxysilanes on the surface of the core, or Partially condensed organofunctional silanes, mixtures of two or more organofunctional silanes, or mixtures of one or more organofunctional silanes with a tetraalkoxysilane (i.e., tetraethoxysilane, tetramethoxysilane) are applied to the surface of the core.

[0166] In other respects, the hybrid material may independently comprise from about 0 mol% to 100 mol% of the hybrid material. The inorganic portion of the surrounding material may independently be alumina, silicon dioxide, titanium dioxide, cerium oxide, zirconium oxide, or ceramic materials or mixtures thereof.

[0167] In certain aspects, the inorganic portion of the hybrid material may be present independently in an amount ranging from about 0 mol% to no more than about 25 mol%, wherein the pores of the surrounding material are substantially disordered. Similarly, the inorganic portion of the surrounding material may be present independently in an amount ranging from about 25 mol% to no more than about 50 mol%, wherein the pores of the surrounding material are substantially disordered, and wherein the hybrid layer material may or may not independently possess pore geometry characteristics (CEPG) that are chromatographically enhanced. In some embodiments, the inorganic portion of the hybrid layer material may be present independently in an amount ranging from about 50 mol% to no more than about 75 mol%, wherein the pores of the hybrid layer material are substantially disordered, and wherein the hybrid layer material independently possesses pore geometry characteristics (CEPG) that are chromatographically enhanced. In other embodiments, the inorganic portion of the hybrid layer material may be present independently in an amount ranging from about 75 mol% to no more than about 100 mol%, wherein the pores of the hybrid layer material are substantially disordered, and wherein the hybrid layer material may or may not independently possess pore geometry characteristics (CEPG) that are chromatographically enhanced.

[0168] In other aspects, the inorganic portion of the hybrid material can independently range from about 0 mol% to no more than about 100 mol%; specifically, 0% to 10%, 0% to 5%, 0% to 4%, 0% to 3%, 0% to 2%, 0% to 1%, 1% to 10%, 1% to 5%, 1% to 4%, 1% to 3%, 1% to 2%, 5% to 100%, 10% to 100%, 15% to 100%, 20% to 100%, 25% to 100%, 30% to 100%, 35% to 100%, 40% to 100%, 45% to 100%, 55% to 100%, 60% to 100%, 65%. The quantity is present in the range of 100%, 70% to 100%, 75% to 100%, 80% to 100%, 81% to 100%, 82% to 100%, 83% to 100%, 84% to 100%, 85% to 100%, 86% to 100%, 87% to 100%, 88% to 100%, 89% to 100%, 90% to 100%, 91% to 100%, 92% to 100%, 93% to 100%, 94% to 100%, 95% to 100%, 96% to 100%, 97% to 100%, 98% to 100%, or 99% to 100%.

[0169] In some respects, hybrid materials may include materials of formula I: (SiO2) d / [R 2 ((R) p (R 1 ) q SiO t ) m ]; (I) in, R and R 1 Each independently is C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C18 Aryl, C1-C 18 heteroaryl; or absent; wherein each R 2 is connected to two or more silicon atoms; p and q are each independently 0.0 to 3.0, t is 0.5, 1.0, or 1.5; d is 0 to about 30; m is an integer from 1 to 20; wherein R, R 1 and R 2 are optionally substituted; Provided that: (1) When R 2 is absent, m = 1, and when 0 < p + q ≤ 3, ; and (2) When R 2 is present, m = 2 to 20, and when p + q ≤ 2, .

[0170] In other aspects, the hybrid layer material may include a material of formula II: (SiO2) d [[ID=​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​​t ) m (III) in, R 1 For C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C1-C 18 heteroaryl; or nonexistent; where each R 2 Connected to two or more silicon atoms; d ranges from 0 to approximately 30; r can be 0, 1, or 2, provided that when r = 0, then t = 1.5; when r = 1, then t = 1; or when r = 2, then t = 0.5; and m is an integer from 1 to 20.

[0172] In other respects, hybrid materials may include materials of formula IV: (A) x (B) y (C) z (IV) The repeating units A, B, and C can be arranged randomly, in blocks, or a combination of random and blocks. A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit that is bonded to one or more repeating units B or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds. C is an inorganic repeating unit bonded to one or more repeating units B or C via inorganic bonds; and x and y are positive numbers, and z is a non-negative number, where x + y + z = 1. In some implementations, when z = 0, then 0.002 ≤ x / y ≤ 210, and when z ≠ 0, then 0.0003 ≤ y / z ≤ 500 and 0.002 ≤ x / (y + z) ≤ 210.

[0173] In other respects, hybrid materials may include materials of formula V: (A)x(B)y(B*)y*(C)z(V), The repeating units A, B, B* and C can be arranged as random, segmented, or a combination of random and segmented. A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit that is bonded to one or more repeating units B or B* or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds. B* is an organosiloxane repeating unit that is bonded to one or more repeating units B or B* or C via inorganic siloxane bonds, wherein B* is an organosiloxane repeating unit that is a non-reactive (i.e., polymerizable) organic component and may further have protected functional groups that can be deprotected after polymerization. C is an inorganic repeating unit bonded to one or more repeating units B or B* or C via inorganic bonds; and x and y are positive numbers, and z is a non-negative number, where x + y + y* + z = 1. In some implementations, when z = 0, then 0.002 ≤ x / (y + y*) ≤ 210, and when z ≠ 0, then 0.0003 ≤ (y + y*) / z ≤ 500 and 0.002 ≤ x / (y + y* + z) ≤ 210.

[0174] In some respects, R in the above formula 2 It may exist or it may not exist.

[0175] In some respects, R in the above formula 1 It is a C1-C substituted with a hydroxyl group. 18 Alkyl groups. In other respects, R in the formulas shown above... 1 It is hydroxypropyl. In other respects, the hydroxyl-substituted alkyl group is further functionalized with isocyanate. In still other respects, the isocyanate is octadecyl isocyanate, dodecyl isocyanate, pentafluorophenyl isocyanate, 4-cyanophenyl isocyanate, 3-cyanophenyl isocyanate, 2-cyanophenyl isocyanate, phenyl isocyanate, benzyl isocyanate, phenethyl isocyanate, or diphenylethyl isocyanate.

[0176] In some embodiments, the organosiloxane is, but is not limited to, phenyltriethoxysilane; phenyltrimethoxysilane; phenethyltriethoxysilane; phenethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane; diethyldiethoxysilane; diethyldimethoxysilane; 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene. 1,3-Bis(trimethoxysilyl)benzene; 1,8-Bis(triethoxysilyl)octane; 1,8-Bis(trimethoxysilyl)octane; 1,2-Bis(trimethoxysilyl)ethane; 1,2-Bis(methyldiethoxysilyl)ethane; 1,2-Bis(methyldiethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane Silane; 1,2-bis(triethoxysilyl)ethylene; 1,2-bis(trimethoxysilyl)ethylene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4-bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; 1,3-bis(trimethoxysilylethyl)benzene; hexyltriethoxy 3,3,3-trifluoropropyltrimethoxysilane; hexyltrimethoxysilane; chloropropyltriethoxysilane; chloropropyltrimethoxysilane; octadecyltrimethoxysilane; octadecyltriethoxysilane; octyltrimethoxysilane; octyltriethoxysilane; 3,3,3-trifluoropropyltrimethoxysilane; 3,3,3-trifluoropropyltriethoxysilane; 3-cyanobutyltriethoxysilane; and 3-cyanobutyltrimethoxysilane, alone or in mixtures with tetraethoxysilane or tetramethoxysilane.

[0177] In another embodiment, the organosiloxane is, but is not limited to, a substituted benzene, including but not limited to 1,4-bis(triethoxysilyl)benzene, 1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene, 1,3,5-tri(triethoxysilyl)benzene, 1,3,5-tri(trimethoxysilyl)benzene, and bis(4-triethoxysilylphenyl)diethoxysilane.

[0178] In another aspect, the present invention provides materials as described herein, wherein the hybrid layer material further comprises one or more nanoparticles dispersed within the core.

[0179] In some embodiments, the nanoparticles are present as <20% by weight of the nanocomposite material, <10% by weight of the nanocomposite material, or <5% by weight of the nanocomposite material.

[0180] In other embodiments, the nanoparticles are crystalline or amorphous and may be silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, their oxides, or their nitrides. In a particular embodiment, the nanoparticles are a substance comprising one or more portions selected from: nanodiamond, silicon carbide, titanium dioxide, cubic boron nitride.

[0181] In other embodiments, the nanoparticles may have a diameter of 200 nm or less, 100 nm or less, 50 nm or less, or 20 nm or less.

[0182] Inorganic chromatographic surface materials In some embodiments, the chromatographic surface material is an inorganic material. In specific embodiments, the inorganic surface material may be an oxide or nitride of diamond, carbon black, graphite, carbon nanotubes, silicon carbide, or aluminum, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, or boron.

[0183] Composite chromatographic surface materials In some embodiments, the chromatographic surface material is a composite material. The term "composite material" describes the engineered material of the invention, consisting of one or more components described herein combined with dispersed nanoparticles, wherein each component / nanoparticle remains separated and isolated at a macroscopic level within the final structure. The composite materials of the invention are form-independent and can be integral or particulate in nature. Furthermore, this document uses the term Np / (A) to describe composite materials containing dispersed nanoparticles. w (b) x (C) y The simplified form of the convention can be understood as follows: the symbol to the left of the slash indicates a dispersed nanoparticle, and the symbol to the right of the slash indicates a component of material in which nanoparticles (indicated to the left of the slash) are dispersed. In some embodiments, the composite material of the present invention may be a nanocomposite material, which is known to include at least, for example, nano / nanotype, internal type, intermediate type, and internal / intermediate type (Nanocomposites Science and Technology, edited by PMAjayan, LS Schadler, PV Braun, Wiley-VCH (Weinheim, Germany), 2003). The term "nanoparticle" is a microscopic member that may be crystalline or amorphous microparticles / abrasives or powders / nanopowders, and at least one size is less than about 100 nm, for example, a diameter or particle thickness of less than about 100 nm (0.1 µm).

[0184] Nanoparticles possess properties that differ from and are generally superior to conventional bulk materials, including, for example, greater strength, hardness, ductility, sinterability, and activity. Extensive scientific research continues to focus on determining the properties of nanomaterials, and a small number of nanomaterials have been synthesized (primarily as nanoscale powders) through various methods, including colloidal precipitation, mechanical milling, and vapor-phase nucleation and growth. Extensive reviews document the latest developments in nanophase materials and are incorporated herein by reference: Gleiter, H. (1989) “Nano-crystalline materials,” Prog. Mater. Sci. 33:223-315 and Siegel, RW (1993) “Synthesis and properties of nano-phase materials,” Mater. Sci. Eng. A168:189-197. In some embodiments, the nanoparticles comprise oxides or nitrides of silicon carbide, aluminum, diamond, cerium, carbon black, carbon nanotubes, zirconium, barium, cerium, cobalt, copper, europium, gadolinium, iron, nickel, samarium, silicon, silver, titanium, zinc, boron, and mixtures thereof. In some embodiments, the nanoparticles of the present invention are selected from diamond, zirconium oxide (amorphous, monoclinic, tetragonal, and cubic), titanium dioxide (amorphous, anatase, brookite, and rutile forms), aluminum (amorphous, α, and γ forms), and boron nitride (cubic form). In particular embodiments, the nanoparticles of the present invention are selected from nanodiamond, silicon carbide, titanium dioxide (anatase form), cubic boron nitride, and any combination thereof. Furthermore, in particular embodiments, the nanoparticles may be crystalline or amorphous. In particular embodiments, the nanoparticles have a diameter less than or equal to 100 nm, for example, less than or equal to 50 nm, for example, less than or equal to 20 nm.

[0185] Furthermore, it should be understood that nanoparticles characterized by dispersion within the composites of the present invention are intended to describe exogenously added nanoparticles. This differs from nanoparticles capable of in-situ formation, or formations that are significantly similar to presumed nanoparticles, wherein, for example, macromolecular structures such as particles may contain aggregates of these formed endogenously.

[0186] Nanoparticles are of great scientific interest because they can serve as effective bridges between bulk materials and atomic or molecular structures. Bulk materials should possess constant physical properties, independent of size, but this is not always the case at the nanoscale. Size-dependent properties have been observed, such as quantum confinement in semiconductor particles, surface plasmon resonances in some metal particles, and superparamagnetism in magnetic materials.

[0187] In some embodiments, the composite material includes magnetic materials, materials with high thermal conductivity, or mixtures thereof.

[0188] Materials, cores, or additives with high thermal conductivity are defined as materials, cores, or additives used in porous surface particles with a thermal conductivity greater than 20 W / (m·K). In various embodiments, the core or additive has a thermal conductivity in the following ranges: about 20 W / (m·K) to no more than 3500 W / (m·K); about 100 W / (m·K) to no more than 3300 W / (m·K); and 400 W / (m·K) to no more than 3000 W / (m·K). The high thermal conductivity core or additive may be a core particle of 0.1 µm to 8 µm, a nanoparticle additive, or a metal oxide precursor. In various embodiments, the high thermal conductivity core or additive includes (but is not limited to) aluminum, copper, gold, and diamond.

[0189] High thermal diffusivity additives are defined as those with a thermal diffusivity greater than 20 mm. 2 The additive used in the surface porous particles of / s. In various embodiments, the additive has a thermal diffusivity range of approximately 20 mm. 2 / s to no more than 2000mm 2 / s; approximately 100mm 2 / s to no more than 1600mm 2 / s; and 150mm 2 / s to no more than 1400mm 2 / s. The high thermal conductivity additive can be a core particle from 0.1µm to 8µm, a nanoparticle additive, or a metal oxide precursor. In various embodiments, the high thermal conductivity additive includes (but is not limited to) aluminum, copper, gold, and diamond.

[0190] Magnetic materials include those with a strength greater than 15 emu / g (A m) at room temperature. 2 Materials with a magnetic susceptibility (σ, magnetic moment per unit mass, magnetic saturation or saturation magnetization) of 1 / kg. This includes ferromagnetic and ferrimagnetic materials, including (but not limited to): magnetite (magnetic iron oxide); hematite; yttrium iron garnet, cobalt, CrO2; and ferrites containing iron and Al, Mg, Ni, Zn, Mn or Co. Magnetic core particles do not include other iron oxides, including hematite and goethite with magnetic susceptibility values ​​less than 10 emu / g. Hematite (0.4 emu / g) is considered antiferromagnetic at room temperature.

[0191] Surface materials of ionizable modifiers In some embodiments of the present invention, a chromatographic material with controlled porosity is provided, comprising one or more layers of a chromatographic surface material, wherein the chromatographic surface material contains hydrophobic surface groups and one or more ionizable modifiers. In some embodiments, the ionizable modifiers do not contain zwitterionic or quaternary ammonium ion portions.

[0192] Those skilled in the art can modify the composition of chromatographic surface materials and core materials (if present) to provide enhanced chromatographic selectivity, enhanced column chemical stability, enhanced column efficiency, and / or enhanced mechanical strength. Similarly, the composition of the surrounding materials provides changes in hydrophilic / lipophilic balance (HLB), surface charge (e.g., isoelectric point or silanol pKa), and / or surface functionality to enhance chromatographic separation. Furthermore, in some embodiments, the composition of the chromatographic materials may also provide surface functionality that can be used for further surface modification.

[0193] The ionizable modifiers and hydrophobic surface groups of the chromatographic surface materials of the present invention can be prepared using known methods. Some ionizable modifier reagents are commercially available. For example, silanes having aminoalkyltrialkoxysilanes, methylaminoalkyltrialkoxysilanes, and pyridylalkyltrialkoxysilanes are commercially available. Other silanes such as chloropropylalkyltrichlorosilanes and chloropropylalkyltrialkoxysilanes are also commercially available. These can be reacted with imidazole bonds to produce imidazole alkylsilyl surface materials; or reacted with pyridine bonds to produce pyridylalkylsilyl surface materials. Other acid modifiers are also commercially available, including but not limited to sulfopropyltrisilanol, carboxyethylsilanetriol, 2-(methyl ester)ethylmethyldichlorosilane, 2-(methyl ester)ethyltrichlorosilane, 2-(methyl ester)ethyltrimethoxysilane, n-(trimethoxysilylpropyl)ethylenediaminetriacetic acid, (2-diethylphosphorylethyl)triethoxysilane, 2-(chlorosulfonylphenyl)ethyltrichlorosilane, and ethyl-2-(chlorosulfonylphenyl)ethyltrimethoxysilane.

[0194] Those skilled in the art are familiar with the synthesis of these types of silanes using common synthetic methods, including Grignard reactions and hydrosilylation. The products can be purified by chromatography, recrystallization, or distillation.

[0195] Other additives, such as isocyanates, are commercially available or can be synthesized by those skilled in the art. A common isocyanate formation scheme involves the reaction of a primary amine with phosgene, or triphosgene, as a reagent.

[0196] In some embodiments, the ionizable modifier comprises a carboxylic acid group, a sulfonic acid group, a phosphate group, a boric acid group, an amino group, an imino group, an amide group, a pyridyl group, an imidazole group, a urea group, a thionyl-urea group, or an aminosilyl group.

[0197] In other respects, ionizable modifiers can be selected from the group having the following formula: Formula (I) Equation (II): Equation (III): in m is an integer from 1 to 8; v is 0 or 1; When v is 0, m' is 0; When v is 1, m' is an integer from 1 to 8; Z represents a chemically reactive group, including (but not limited to) [a specific group]. -OH, -OR 6 Amines, alkylamines, dialkylamines, isocyanates, acyl chlorides, trifluoromethanesulfonates, isocyanates, thiocyanates, imidazole carbonates, NHS-esters, carboxylic acids, esters, epoxides, alkynes, alkenes, azides, -Br, -Cl, or -I; Y represents an embedded polar functional group; R 1 Each occurrence independently represents a chemically reactive group on silicon, including (but not limited to) -H, -OH, -OR. 6 Dialkylamines, trifluoromethanesulfonates, Br, Cl, I, vinyl groups, alkenes, or -(CH2) m” Q; Q is -OH or -OR each time it appears. 6 Amines, alkylamines, dialkylamines, isocyanates, acyl chlorides, trifluoromethanesulfonates, isocyanates, thiocyanates, imidazole carbonates, NHS-esters, carboxylic acids, esters, epoxides, alkynes, alkenes, azides, -Br, -Cl, or -I; "m" is an integer from 1 to 8; p is an integer from 1 to 3; R 1’ Each occurrence is independently represented by F, C1-C. 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Heteroaryl, fluoroalkyl, or fluoroaryl; R 2R 2’ R 3 and R 3’ Each time it appears, it independently represents hydrogen, C1-C. 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C2-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C4-C 18 heteroaryl, -Z, or having the formula -Si(R') b R” a Or -C(R') b R” a group; a and b each represent integers from 0 to 3, provided that a + b = 3; R' represents a C1-C6 straight-chain, cyclic, or branched alkyl group; R” is a functionalized group selected from alkyl, alkenyl, alkynyl, aryl, cyano, amino, glycol, nitro, ester, cationic or anion exchange group, or an alkyl or aryl group containing an embedded polar functional group and a chiral moiety. R 4 Indicates hydrogen, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 5 Indicates hydrogen, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 6 Each occurrence is represented independently as C1-C. 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; Het represents a heterocyclic or heteroaryl ring system containing at least one nitrogen atom; and A represents either the acidic ionizable modifier portion or the doubly charged ionizable modifier portion.

[0198] In other embodiments, the ionizable modifier is aminopropyltriethoxysilane, aminopropyltrimethoxysilane, 2-(2-(trichlorosilyl)ethyl)pyridine, 2-(2-(trimethoxy)ethyl)pyridine, 2-(2-(triethoxy)ethyl)pyridine, 2-(4-pyridylethyl)triethoxysilane, 2-(4-pyridylethyl)trimethoxysilane, 2-(4-pyridylethyl)trichlorosilane, chloropropyltrimethoxysilane, chloropropyltrichlorosilane, chloropropyltrichlorosilane, chloropropyltriethoxysilane, imidazolylpropyltrimethoxysilane, imidazolylpropyltriethoxysilane, imidazolylpropyltrichloro ... Silanes, sulfonyltrisilane, carboxyethylsilanetriol, 2-(methyl ester)ethylmethyldichlorosilane, 2-(methyl ester)ethyltrichlorosilane, 2-(methyl ester)ethyltrimethoxysilane, n-(trimethoxysilylpropyl)ethylenediaminetriacetic acid, (2-diethylphosphorylethyl)triethoxysilane, 3-mercaptopropyltriethoxysilane, 3-mercaptopropyltrimethoxysilane, bis[3-(triethoxysilyl)propyl]disulfide, bis[3-(triethoxysilyl)propyl]tetrasulfide, 2,2-dimethoxy-1-thia-2-silazopentanane, bis(trichlorosilylethyl)phenylsulfonyl chloride, 2-(chlorosulfonylphenyl)ethyltrichlorosilane, 2-(chlorosulfonylphenyl)ethyltrimethoxysilane, 2-(ethoxysulfonylphenyl)ethyltrimethoxysilane, 2-(ethoxysulfonylphenyl)ethyltrimethoxysilane, 2-(ethoxysulfonylphenyl)ethyltrichlorosilane, phenylethyltrisilanol sulfonic acid, diethyl phenylphosphonate (triethoxysilylethyl)phenylphosphonate, diethyl phenylphosphonate (trimethoxysilylethyl)phenylphosphonate, diethyl phenylphosphonate (trichlorosilylethyl)phenylphosphonate, phenylethyltrisilanol phosphate, N-(3-trimethoxysilylpropyl)pyrrole, N-(3-triethoxysilylpropyl)-4 5-Dihydroimidazole, bis(methyldimethoxysilylpropyl)-N-methylamine, tris(triethoxysilylpropyl)amine, bis(3-trimethoxysilylpropyl)-N-methylamine, (N,N-diethyl-3-aminopropyl)trimethoxysilane, N-(hydroxyethyl)-N-methylaminopropyltrimethoxysilane, 3-(N,N-dimethylaminopropyl)trimethoxysilane, bis(2-hydroxyethyl)-3-aminopropyltriethoxysilane, N,N'-bis(hydroxyethyl)-N,N'-bis(trimethoxysilylpropyl)ethylenediamine, or N,N-dimethyl-3-aminopropylmethyldimethoxysilane.

[0199] In some embodiments, when the ionizable modifier is of formula (III), the acidic ionizable modifier is a protected or deprotected form of trisilane, trialkoxysilane, or trichlorosilane; or a salt of sulfonic acid alkylsilane, sulfonic acid phenylalkylsilane, sulfonic acid benzylalkylsilane, sulfonic acid phenylsilane, sulfonic acid benzylsilane, carboxylic acid alkylsilane, carboxylic acid phenylalkylsilane, carboxylic acid benzylalkylsilane, carboxylic acid phenylsilane, carboxylic acid benzylsilane, phosphate alkylsilane, phosphonic acid phenylalkylsilane, phosphonic acid benzylalkylsilane, phosphonic acid phenylsilane, phosphonic acid benzylsilane, borate alkylsilane, borate phenylalkylsilane, borate benzylalkylsilane, borate phenylsilane, or borate benzylsilane.

[0200] In some embodiments, when the ionizable modifier is of formula (III), the acidic ionizable modifier is a sulfonic acid alkyl isocyanate, a sulfonic acid phenyl alkyl isocyanate, a sulfonic acid benzyl alkyl isocyanate, a sulfonic acid phenyl isocyanate, a sulfonic acid benzyl isocyanate, a carboxylic acid alkyl isocyanate, a carboxylic acid benzyl alkyl isocyanate, a carboxylic acid benzyl alkyl isocyanate, a carboxylic acid benzyl isocyanate, a carboxylic acid benzyl isocyanate, a phosphate alkyl isocyanate, a phosphonic acid phenyl alkyl isocyanate, a phosphonic acid benzyl alkyl isocyanate, a phosphonic acid benzyl isocyanate, a borate alkyl isocyanate, a borate phenyl alkyl isocyanate, a borate benzyl alkyl isocyanate, a borate benzyl alkyl isocyanate, a borate benzyl isocyanate, a borate benzyl isocyanate, or a protected or deprotected form or salt of borate benzyl isocyanate.

[0201] In some embodiments, when the ionizable modifier is selected from formula (III), A represents a bicharged ionizable modifier moiety. Although not theoretically limited, the bicharged ionizable modifier moiety has two subgroups that can exhibit opposite charges. Under some conditions, the bicharged ionizable modifier moiety can similarly act as both a zwitterion and a zwitterionic electrolyte, exhibiting both positive and negative charges while maintaining a net charge of zero. Under other conditions, the bicharged ionizable modifier moiety may have only one ionizing group and may exhibit either a net positive or negative charge. The bicharged ionizable modifier moiety includes, but is not limited to: alkyl; branched alkyl; aryl; cyclic, polyaromatic, polycyclic, heterocyclic, and polyheterocyclic groups that can exhibit a positive charge (typically on a nitrogen or oxygen atom) and a negative charge through an acidic group including a carboxyl, sulfonic, phosphonic, or boric acid group. Alternatively, some metal-containing complexes can exhibit both positive and negative charges. The doubly charged ionizable modifier portion may also include, but is not limited to, zwitterions, amphoteric electrolytes, amino acids, aminoalkyl sulfonic acids, aminoalkyl carboxylic acids, mono- and di-methylaminoalkyl sulfonic acids, mono- and di-methylaminoalkyl carboxylic acids, pyridinealkyl sulfonic acids, and pyridinealkyl carboxylic acid groups. Alternatively, the doubly charged ionizable modifier portion may be 2-(N-morpholino)ethanesulfonic acid, 3-(N-morpholino)propanesulfonic acid, 4-(2-hydroxyethyl)-1-piperazine ethanesulfonic acid, piperazine-N,N'-bis(2-ethanesulfonic acid), N-cyclohexyl-3-aminopropanesulfonic acid, N-cyclohexyl-2-hydroxy-3-aminopropanesulfonic acid, 3-[(3-cholamidopropyl)dimethylamine]-1-propanesulfonate, 6-methyl-9,10-disodehydro-ergoline-8-carboxylic acid, phenol sulfonphthalein, betaine, quinone compounds, N,N-bis(2-hydroxyethyl)glycine, and N-[tris(hydroxymethyl)methyl]glycine group.

[0202] In some embodiments, the molar ratio of hydrophobic surface groups to ionizable modifier in the surface material of the present invention is about 4:1 to about 150:1; about 20:1 to about 100:1; or about 25:1 to about 100:1.

[0203] In other embodiments, the concentration of the ionizable modifier in the surface material of the present invention is less than about 0.5 µmol / m 2 Less than approximately 0.4 µmol / m 2 Less than approximately 0.3 µmol / m 2 Approximately 0.01 µmol / m 2 To approximately 0.5 µmol / m 2 Approximately 0.1 µmol / m 2 To approximately 0.4 µmol / m 2 or approximately 0.2 µmol / m 2 To approximately 0.3 µmol / m 2 .

[0204] In another aspect, the surface material of the present invention has a quantified surface coverage ratio B / A of about 2.5 to about 300, wherein A represents an ionizable modifier and B represents a hydrophobic group. In some aspects, the quantified surface coverage ratio B / A is about 3 to about 200, about 4 to about 35, or about 5 to about 22.

[0205] In another aspect, the hydrophobic surface groups of the surface material of the present invention are C4 to C18 bonded phases. In some aspects, the hydrophobic surface groups are C18 bonded phases. In other aspects, the hydrophobic surface groups are embedded polar bonded phases. In still other aspects, the hydrophobic surface groups are aromatic phenylalkyl, fluoro-aromatic phenylhexyl, or pentafluorophenylalkyl bonded phases. In another aspect, the hydrophobic surface groups are C4-C18 bonded phases. 30 Intercalated with polar, chiral phenylalkyl groups or pentafluorophenyl groups bonded or coated.

[0206] Core and material form Further improvements in permeability can be achieved by changing the particle shape. For example, a highly spherical core can be replaced with a uniform micron-sized annular, rod-shaped, dumbbell-shaped, star-shaped, or bent rod-shaped core. Additional shapes include (but are not limited to) spirals, discs, concave discs, coils, rings, helical shapes, saddle-shaped shapes, cross-shaped shapes, cubic shapes, derby shapes, cylinders, and tubes. Examples of dumbbell-shaped, ring-shaped, rod-shaped, helical, and helical icosahedral particles have been reported (Doshi, N. PNAS, 2009, 106, 51, 21495; Alexander, L. Chem. Commun., 2008, 3507; Naik, SJPhys. Chem.C 2007, 111, 11168; Pang, X. Microporous and Mesoporous Materials 85 (2005) 1; Kievsky, Y. IEEE Transactions on Nanotechnology, 2005, 4, 5, 490; Sugimoto, T. in Monodispersed Particles, (Elsevier Science BV, Amsterdam) 2001; Ozin, G. Adv. Mater., 1997, 9, 662).

[0207] The key factors for non-spherical cores are their relative size uniformity, free flow, lack of pores, and mechanical strength sufficient for use in HPLC and UPLC. The components of these cores can be selected from (but are not limited to) silica, metal oxides, diamond, highly cross-linked polymers, and hybrid materials. Improved core uniformity can be achieved through gradation. Reduced porosity can be achieved by filling the pores with similar or different components (e.g., pore-filling silica material with cross-linked polymer components). Improved mechanical strength can be achieved by increasing cross-linking with the same or different components (e.g., creating a silica network within the polymer composition) or by calcination. For the latter, higher temperatures (e.g., >800°C) can be advantageously used.

[0208] To reduce unwanted chromatographic interactions attributable to the core, a non-porous surface coated with silica, a hybrid, or a polymer composition can be advantageously used. This surface coating step may need to be repeated or performed during growth to achieve the desired thickness. To ensure that the core morphology remains substantially unchanged, this step advantageously provides a uniform surface layer. Calcination and surface re-hydroxylation can be advantageously utilized at the end of this step.

[0209] Uniform silica or hybrid surface porous layers can be formed by any of the methods described herein. This step advantageously yields a highly uniform porous layer to ensure that the core morphology remains substantially unchanged. Subsequently, additional steps such as fractionation, calcination, pore modification, recalcination, rehydroxylation, and bonding are performed (as needed), as detailed above. These non-spherical surface porous materials can be packed into chromatographic columns independently or as a mixture with other shapes or with spherical particles. Optimizing the column packing conditions for these mixed systems is important. Bulk density and sedimentation rate between different materials are required to maintain similar dispersibility.

[0210] Therefore, in some embodiments, the core material of the present invention has a specific core morphology. In some embodiments, such a core morphology is produced by using a core with a defined shape. In some other embodiments, the core morphology refers to a specific defined shape of the product material of the present invention.

[0211] In some embodiments, the core or product material has a highly spherical, rod-shaped, bent rod-shaped, annular, or dumbbell-shaped core morphology.

[0212] In some other embodiments, the core or product material is a mixture of highly spherical, rod-shaped, bent rod-shaped, annular, or dumbbell-shaped core morphologies.

[0213] Material properties: Compared to fully porous silica particles of the same size, the materials of this invention can exhibit significantly higher thermal conductivity. In some embodiments, the surface-porous materials of this invention exhibit significantly higher thermal conductivity compared to surface-porous silica particles of the same size. Considering the differences in bulk material properties, pore volume, type of surface modification, and coverage, this can be achieved through Gritti and Guiochon […]. J. Chromatogr. The particle thermal conductivity was determined using the method described in A, 2010, 1217, 5137.

[0214] Compared to fully porous silica particles of the same size, the materials of the present invention exhibit significantly modified chemical stability when exposed to unbound high-pH mobile phases. In some embodiments, the surface-porous materials of the present invention exhibit significantly modified chemical stability when exposed to unbound high-pH mobile phases, compared to surface-porous silica particles of the same size.

[0215] Compared to fully porous silica particles of the same size, the material of the present invention can form a packed bed with improved permeability. In some embodiments, the surface-porous material of the present invention can form a packed bed with improved permeability compared to surface-porous silica particles of the same size. Improved permeability for a given particle size is observed when the column back pressure decreases. The permeability of the packed bed can be determined by reversed-phase size exclusion chromatography.

[0216] The material (which is particles) has an average particle size between 0.8 µm and 3.0 µm. Specifically, the average particle size of the material may be between 1.1 µm and 2.9 µm or between 1.3 µm and 2.7 µm.

[0217] The material has pores with an average diameter of about 25 Å to 600 Å; about 60 Å to 350 Å; about 80 Å to 300 Å; or about 90 Å to 150 Å.

[0218] The material has a diameter of approximately 0.11 cm. 3 / g to 0.50cm 3 / g; approximately 0.09cm 3 / g to 0.45cm 3 / g; or approximately 0.17cm 3 / g to 0.30cm 3 / g average pore volume.

[0219] The material has approximately 10m 2 / g to 400m 2 / g of pore surface area.

[0220] Surface modification and bonding The materials of this invention can also undergo further bonding or surface modification.

[0221] Therefore, in one embodiment, the material of the present invention may incorporate a bonded phase. In some such embodiments, the bonded phase is a C4 to C18 bonded phase. In a particular aspect, the bonded phase is a C18 bonded phase. In other aspects, the bonded phase has an embedded polar bonded phase. In other aspects, the bonded phase is an aromatic phenylalkyl, fluoro-aromatic phenylhexyl, or pentafluorophenylalkyl bonded phase. In another aspect, the bonded phase is C4-C 30 Intercalated with polar, chiral phenylalkyl groups or pentafluorophenyl groups bonded or coated.

[0222] In another embodiment, the material as described herein may be available with formula Z a (R') b Surface modification is performed using a surface modifier called Si-R", where Z = Cl, Br, I, C1-C5 alkoxy, dialkylamino, or trifluoromethanesulfonate; a and b are each integers from 0 to 3, provided that a+b=3; R' is a C1-C6 straight-chain, cyclic, or branched alkyl group, and R” is a functionalized group.

[0223] In another embodiment, the material is surface-modified by coating a polymer.

[0224] In some embodiments, R' is selected from methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, pentyl, isopentyl, hexyl, and cyclohexyl. In other embodiments, R is selected from alkyl, alkenyl, alkynyl, aryl, cyano, amino, glycol, nitro, ester, cation or anion exchange group, or alkyl or aryl group comprising an embedded polar functional group and a chiral moiety. In some embodiments, R' is selected from aromatic phenylalkyl, fluoroaromatic phenylhexyl, pentafluorophenylalkyl, and a chiral moiety.

[0225] In one implementation, R” is C1-C 30 Alkyl group. In another embodiment, R” comprises a chiral moiety. In yet another embodiment, R” is C1-C 20 Alkyl groups.

[0226] In some embodiments, the surface modifier comprises embedded polar functional groups. In some embodiments, such embedded polar functional groups include carbonates, amides, urea, ethers, thioethers, sulfinyl groups, sulfonyl groups, thiourea groups, thiocarbonates, thiocarbamates, ethylene glycol, heterocyclic or triazole functional groups. In other embodiments, such embedded polar functional groups include carbamate functional groups (such as those disclosed in U.S. Patent 5,374,755) and chiral moieties. Such groups include those of the following general formulas: Where l, m, o, r, and s are 0 or 1, n is 0, 1, 2, or 3, p is 0, 1, 2, 3, or 4, and q is an integer from 0 to 19; R3 is selected from hydrogen, alkyl, cyano, and phenyl; and Z, R', a, and b are as defined above. Advantageously, the urethane functional group has the following general formula structure: Where R 5 It can be, for example, cyanoalkyl, tert-butyl, butyl, octyl, dodecyl, tetradecyl, octadecyl, or benzyl. Advantageously, R 5 It is octyl, dodecyl, or octadecyl.

[0227] In some embodiments, the surface modifier is selected from phenylhexyltrichlorosilane, pentafluorophenylpropyltrichlorosilane, octyltrichlorosilane, octadecyltrichlorosilane, octyldimethylchlorosilane, and octadecyldimethylchlorosilane. In some embodiments, the surface modifier is selected from octyltrichlorosilane and octadecyltrichlorosilane. In other embodiments, the surface modifier is selected from isocyanates or 1,1'-carbonyldiimidazoles (especially when the hybrid group includes a (CH2)3OH group).

[0228] In another embodiment, the material is surface-modified by a combination of organic groups and silanol groups.

[0229] In yet another embodiment, the material is surface-modified through a combination of organic group modification and coating polymer. In yet another embodiment, the organic group comprises a chiral moiety.

[0230] In yet another embodiment, the material is surface-modified by a combination of silanol modification and coating polymer.

[0231] In other embodiments, the material is surface modified by forming organic covalent bonds between the organic groups of the particles and the modifying agent.

[0232] In other embodiments, the material is surface modified by a combination of organic group modification, silanol group modification, and coating polymer.

[0233] In another embodiment, the material is surface-modified by silanol modification.

[0234] Preparation method This invention provides a method for preparing chromatographic materials with controlled porosity.

[0235] In some embodiments, the present invention provides a method for preparing chromatographic materials having controlled porosity, comprising: a. Provide chromatographic core materials with a main surface; and b. Apply one or more layers of chromatographic surface material to the main surface. To produce chromatographic materials with controlled porosity.

[0236] In other embodiments, the present invention provides a method for preparing chromatographic materials having controlled porosity, comprising: a. Provide chromatographic core materials with a main surface; and b. Apply a chromatographic surface material and an electrolyte to the surface; c. Removing the polymeric electrolyte to form the resulting material with a surface; and d. Optionally repeat steps b and c once or more on the surface of the resulting material. To produce chromatographic materials with controlled porosity.

[0237] In embodiments utilizing polymeric electrolytes, each polymeric electrolyte may independently be a straight-chain, branched, or block polymer comprising one or more alkyl, cycloalkyl, aryl, or ethylene oxide groups and one or more primary, secondary, tertiary, and quaternary amino groups, pyrrolidone groups, pyridine groups, or imidazole groups, wherein each polymeric electrolyte may be positively or negatively charged.

[0238] Subsequently, the polymeric electrolyte can be removed by any method known in the art, including but not limited to calcination, heat treatment, chemical extraction, degradation, and ozone decomposition.

[0239] In some embodiments, the method further includes a post-synthetic processing step, wherein the post-synthetic processing step is end-capping, hydrothermal treatment, extraction, ozone decomposition, lyophilization, pseudomorphic conversion, chromatographic material in an inorganic surrounding material, chromatographic material in an inorganic / organic hybrid surrounding material, drying, heat treatment, dispersion, acid treatment, reaction with hybrid functional groups, surface modification, grinding, classification, sedimentation, or a combination thereof.

[0240] Particularly important in controlling the porosity of the materials of the present invention is the ability to alter the composition, pore size, pore volume, or specific surface area of ​​the individual layers in the chromatographic surface material. This allows porosity to be controlled in a predetermined or desired pattern. In some embodiments, the predetermined pattern may include an increase in average pore size, a decrease in average pore size, an increase in average pore volume, a decrease in average pore volume, an increase in specific surface area, a decrease in specific surface area, or a combination thereof. In such embodiments, the predetermined pattern is generally considered to begin at the main surface of the chromatographic core material and proceed to the outermost surface of the chromatographic material. In some embodiments, the predetermined pattern may be observed from the outermost surface of the chromatogram to the main surface of the chromatographic core material.

[0241] In some embodiments, the predetermined pattern may be conical, tapered, conical, flared, or another predetermined pattern having a single pattern from the core to the outermost surface or a repeating pattern from the core to the outermost surface. Such predetermined patterns can be seen, for example... Figure 20 .

[0242] The following solutions can be used in the method of this invention.

[0243] The method for forming a porous surface material can be used in the method protected by the claims.

[0244] Each layer of the chromatographic surface material is independently selected from porous inorganic / organic hybrid materials, porous silica, porous composite materials, or mixtures thereof. In some embodiments, each layer of the chromatographic core material may be silica; silica coated with an inorganic / organic hybrid surrounding material; magnetic core material; magnetic core material coated with silica; high thermal conductivity core material; high thermal conductivity core material coated with silica; composite material; inorganic / organic hybrid surrounding material; composite material coated with silica; magnetic core material coated with inorganic / organic hybrid surrounding material; or high thermal conductivity core material coated with inorganic / organic hybrid surrounding material.

[0245] In other embodiments, the individual layers of the chromatographic surface material may have the following formula: (SiO2) d / [R 2 ((R) p (R 1 ) q SiO t ) m (I) in, R and R 1 Each independently is C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C18 Aryl, C1-C 18 heteroaryl; or absent; wherein each R 2 is connected to two or more silicon atoms; p and q are each independently 0.0 to 3.0, t is 0.5, 1.0, or 1.5; d is 0 to about 30; m is an integer from 1 to 20; wherein R, R 1 and R 2 are optionally substituted; provided that: (1) when R 2 is absent, m = 1, and when 0 < p + q ≤ 3, ; and (2) when R 2 is present, m = 2 to 20, and when p + q ≤ 2, t = (3-(p+q)) ; Formula: (SiO2) d / [(R) p (R 1 ) q SiO t (II) wherein, R and R 1 are each independently C1-C 18 alkoxy, C1-C 18 alkyl, C1-C[[ID= 54]] 18 alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl, C3-C 18 cycloalkyl, C1-C 18 heterocycloalkyl, C5-C 18 aryl, C5-C 18 aryloxy, or C1-C 18 heteroaryl; d is 0 to about 30; p and q are each independently 0.0 to 3.0, provided that when p + q = 1, then t = 1.5; when p + q = 2, then t = 1; or when p + q = 3, then t = 0.5; Formula: (SiO2) d / [R 2 ((R 1 ) r SiO t ) m (III) wherein, R1 For C1-C 18 Alkoxy, C1-C 18 Alkyl, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C1-C 18 heteroaryl; or nonexistent; where each R 2 Connected to two or more silicon atoms; d ranges from 0 to approximately 30; r can be 0, 1, or 2, provided that when r = 0, then t = 1.5; when r = 1, then t = 1; or when r = 2, then t = 0.5; and m is an integer from 1 to 20; Mode: (A) x (B) y (C) z (IV) The repeating units A, B, and C can be arranged randomly, block, or a combination of random and block; A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit bonded to one or more repeating units B or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds; C is an inorganic repeating unit bonded to one or more repeating units B or C via inorganic bonds; x and y are positive numbers, and z is a non-negative number, where x + y + z = 1. In some embodiments, z = 0, then 0.002 ≤ x / y ≤ 210, and when z ≠ 0, then 0.0003 ≤ y / z ≤ 500 and 0.002 ≤ x / (y + z) ≤ 210; or Mode: (A) x (B) y (B*) y* (C) z (V), The repeating units A, B, B*, and C can be arranged randomly, block, or a combination of random and block; A is an organic repeating unit covalently bonded to one or more repeating units A or B via organic bonds; B is an organosiloxane repeating unit bonded to one or more repeating units B or B* or C via inorganic siloxane bonds and can be further bonded to one or more repeating units A or B via organic bonds; B* is an organosiloxane repeating unit bonded to one or more repeating units B or B* or C via inorganic siloxane bonds, wherein B* is an organosiloxane repeating unit that is a non-reactive (i.e., polymerizable) organic component and may further have protected functional groups that can be deprotected after polymerization; C is an inorganic repeating unit bonded to one or more repeating units B or B* or C via inorganic bonds; x and y are positive numbers, and z is a non-negative number, where x+y+z=1. In some implementations, when z=0, then 0.002≤x / (y+y*)≤210, and when z ≠ 0, then 0.0003≤(y+y*) / z≤500 and 0.002≤x / (y+y*+z)≤210.

[0246] In some embodiments of the invention, sols, polymeric electrolytes, or chemically degradable polymers are used to apply the various layers of the chromatographic surface material, wherein: a) The sol is an inorganic sol, a hybrid sol, nanoparticles, or a mixture thereof; and b) Remove polymeric electrolytes or chemically degradable polymers from materials by chemical extraction, degradation, or heat treatment at temperatures below 500°C, or a combination thereof.

[0247] In some embodiments, the individual layers of the chromatographic surface material are applied by forming electrostatic or acid / base interactions of ionizable groups, including the following steps: a) Prebonding a substantially non-porous core with an alkoxysilane having ionizable groups. b) Treating a substantially non-porous core with a sol, wherein the sol is inorganic hybrid nanoparticles or a mixture thereof, and the pre-bonded alkoxysilanes have ionizable groups with opposite charges to the ionizable groups on the core surface; and c) Forming an additional layer on a material using a sol, which is an inorganic hybrid nanoparticle or a mixture thereof, wherein the pre-bonded alkoxysilane has ionizable groups with opposite charges to the ionizable groups of the preceding layer.

[0248] In certain embodiments, pre-bonding of the core or sol includes washing with an acid or alkali, or a charged polymeric electrolyte. In other embodiments, pre-bonding of the core or sol includes the chemical transformation of available hybrid organic groups.

[0249] In other embodiments, the available hybrid organic group is an aromatic group, which can undergo sulfonation, nitration, amination, or chloromethylation, followed by oxidation or nucleophilic substitution with an amine-containing group to form an ionizable group. In other embodiments, the available hybrid organic group is an olefinic group, which can undergo oxidation, cross-metathesis, or polymerization to form an ionizable group. In a specific embodiment, the available hybrid organic group is a thiol group, which can undergo oxidation, free radical addition, nucleophilic substitution, or polymerization to form an ionizable group.

[0250] In other embodiments, the pre-bonding of the base core or sol includes bonding with an alkoxysilane of Formula 1 having an ionizable group. R(CH2) n Si(Y) 3-x (R') x (Equation 1) Where n = 1 to 30, preferably 2 to 3; x is between 0 and 3; favorablely 0; Y represents chlorine, dimethylamino, trifluoromethanesulfonate, methoxy, ethoxy, or long-chain alkoxy groups; R represents a basic group, including (but not limited to) -NH2, -N(R')H, -N(R')2, -N(R')3 + -NH(CH2) m NH2, -NH(CH2) m N(R')H, -NH(CH2) m N(R')2、-NH(CH2) m N(R')3 + pyridyl, imidazole, polyamine; R' independently represents an alkyl, branched alkyl, aryl, or cycloalkyl group; m ranges from 2 to 6.

[0251] In other embodiments, the pre-bonding of the core or sol includes bonding with an alkoxysilane of formula 2 having an ionizable group. A(CH2) n Si(Y) 3-x (R') x (Equation 2) Where n = 1 to 30, preferably 2 to 3; x is between 0 and 3; favorablely 0; Y represents chlorine, dimethylamino, trifluoromethanesulfonate, methoxy, ethoxy, or long-chain alkoxy groups; A represents an acidic group, including (but not limited to) sulfonic acids, carboxylic acids, phosphoric acids, boric acids, arylsulfonic acids, arylcarboxyl groups, arylphosphonic acids, and arylboronic acids.

[0252] R' independently represents an alkyl, branched alkyl, aryl, or cycloalkyl group.

[0253] In certain implementations, polymeric electrolytes or chemically degradable polymers are used to apply the individual layers of the chromatographic surface material.

[0254] In other embodiments, the polymeric electrolyte or chemically degradable polymer is removed from the material by chemical extraction, degradation, or heat treatment at a temperature below 500°C, or a combination thereof.

[0255] In some embodiments, applying the various layers of the chromatographic surface 1 material using alkoxysilanes, organoalkoxysilanes, nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof includes the following steps: a) In a reaction mixture comprising ethanol, water, and ammonium hydroxide, and optionally containing a nonionic surfactant, an ionic surfactant, a polymeric electrolyte, or a polymer, a siloxane precursor is condensed on a substantially nonporous core to form a chromatographic surface material; and b) Porosity can be introduced through extraction, degradation, oxidation, hydrolysis, deprotection, or transformation of hybrid groups, ionic surfactants, nonionic surfactants, or combinations thereof. In a particular embodiment, alkoxysilanes, organoalkoxysilanes, nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof are condensed on a substantially nonporous core in a solution comprising ethanol, water, ammonium hydroxide, and ionic surfactants; and nonionic surfactants.

[0256] In other embodiments, the ionic surfactant is C 10 -C 30 N(R)3 + X - Where R is methyl, ethyl, propyl, alkyl, or fluoroalkyl; X is a halide, hydroxide ion, or R'SO3. - or R'CO2 - In the form of R', R' is a methyl, ethyl, butyl, propyl, isopropyl, tert-butyl, aryl, tolyl, haloalkyl, or fluoroalkyl group.

[0257] In other embodiments, the ionic surfactant is octadecyltrimethylammonium bromide, octadecyltrimethylammonium chloride, hexadecyltrimethylammonium bromide, hexadecyltrimethylammonium chloride, dodecyltrimethylammonium bromide, or dodecyltrimethylammonium chloride.

[0258] In certain embodiments, the concentration of the ionic surfactant in the reaction solution is maintained between 5 mM and 17 mM; or in some embodiments, between 8 mM and 14 mM.

[0259] In other embodiments, the nonionic surfactant is a diblock or triblock copolymer. In some embodiments, the copolymer is (PEO)x(PPO)y(PEO)x. in PEO is a repeating unit of polyethylene oxide. PPO is a repeating unit of polypropylene oxide. x is an integer between 5 and 106. y is an integer between 30 and 85.

[0260] In a particular embodiment, the triblock copolymer is Pluronic ® P123, has (ΡΕΟ) 20 (PO) 70 (ΡΕΟ) 20 In other embodiments, alkoxysilanes, organoalkoxysilanes, or combinations thereof are condensed in a solution containing the following on a substantially nonporous core: Ethanol, water, ammonium hydroxide, or combinations thereof; Octadecyltrimethylammonium bromide; and Pluronic ® P123.

[0261] In some embodiments, the alkoxysilane used is selected from tetramethoxysilane or tetraethoxysilane.

[0262] In other embodiments, the organosiloxane is selected from phenyltriethoxysilane; phenyltrimethoxysilane; phenethyltriethoxysilane; phenethyltrimethoxysilane; ethyltriethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane; diethyldiethoxysilane; diethyldimethoxysilane; 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(trimethoxysilyl)ethane; 1,2-bis(triethoxysilyl)ethane; 1,2-Bis(triethoxysilyl)ethane; 1,2-Bis(methyldiethoxysilyl)ethane; 1,2-Bis(methyldimethoxysilyl)ethane; Vinyltriethoxysilane; Vinyltrimethoxysilane; Mercaptopropyltrimethoxysilane; Mercaptopropyltriethoxysilane; 1,2-Bis(triethoxysilyl)ethylene; 1,2-Bis(trimethoxysilyl)ethylene; 1,1-Bis(triethoxysilyl)ethane; 1,1-Bis(trimethoxysilyl)ethane; 1,4-Bis(triethoxysilylethyl)benzene; 1,4-Bis(trimethoxysilylethyl)benzene; 1,3-Bis(triethoxysilylethyl)benzene; or 1,3-Bis(trimethoxysilylethyl)benzene.

[0263] In other embodiments, the alkoxysilane used is tetraethoxysilane, and the organoalkoxysilane used is 1,2-bis(triethoxysilyl)ethane.

[0264] In some other embodiments, the concentration of octadecyltrimethylammonium bromide is maintained between 8 mM and 14 mM.

[0265] In some other embodiments, octadecyltrimethylammonium bromide is combined with Pluronic ® The molar ratio of P123 is maintained at 1.30 or higher.

[0266] In other embodiments, the molar ratio of alkoxysilane to organoalkoxysilane ranges from 30:1 to 1:30.

[0267] In some embodiments, the alkoxysilane, organoalkoxysilane, or combinations thereof is pre-diluted with ethanol. In some such embodiments, the pre-diluted ethanol solution of the alkoxysilane, organoalkoxysilane, or combinations thereof is added at a slow and constant rate to prevent particle formation, aggregation, and agglomeration. In other such embodiments, the pre-diluted ethanol solution of the alkoxysilane, organoalkoxysilane, or combinations thereof is added at a rate between 5 µL / min and 500 µL / min.

[0268] In other embodiments, a second solution comprising ethanol, water, ammonium hydroxide, ionic surfactants, and nonionic surfactants is added at a slow and constant rate to prevent particle formation, aggregation, and agglomeration. In some such embodiments, the second solution comprising ethanol, water, ammonium hydroxide, ionic surfactants, and nonionic surfactants is added at a particle surface area (m²) that maintains a uniform ratio. 2 The rate required to maintain a uniform ratio of particle volume (m) to the reaction volume. 3 Add within the range between the required rate and the reaction volume.

[0269] In some embodiments, the surfactant mixture is removed by one or more of the following: extraction with acid, water, or organic solvent; ozone decomposition treatment; heat treatment at <500°C; or heat treatment between 500°C and 1000°C.

[0270] In other embodiments, the surfactant mixture is removed by a combination of acid extraction and ozone decomposition treatment.

[0271] In some embodiments, alkoxysilanes, organoalkoxysilanes, nanoparticles, polyorganoalkoxysiloxanes, or combinations thereof are used to apply various layers of the chromatographic surface material, including the following steps: a) In a reaction mixture containing ethanol, water, or ammonium hydroxide, a siloxane precursor is condensed onto a substantially non-porous core to form a non-porous hybrid inorganic / organic shell material; and b) Porosity is introduced through extraction, degradation, oxidation, hydrolysis, deprotection, or transformation of hybrid groups or combinations thereof.

[0272] In some such embodiments, the alkoxysilane used is selected from tetramethoxysilane or tetraethoxysilane.

[0273] In other such embodiments, the organosiloxane is selected as one or more of the following: phenyltriethoxysilane; phenyltrimethoxysilane; phenethyltriethoxysilane; phenethyltrimethoxysilane; ethyltriethoxysilane; ethyltrimethoxysilane; ethyltrimethoxysilane; methyltriethoxysilane; methyltrimethoxysilane; diethyldiethoxysilane; diethyldimethoxysilane; 1,4-bis(triethoxysilyl)benzene; 1,4-bis(trimethoxysilyl)benzene; 1,3-bis(triethoxysilyl)benzene; 1,3-bis(trimethoxysilyl)benzene; 1,8-bis(triethoxysilyl)octane; 1,8-bis(trimethoxysilyl)octane; 1,2-bis(trimethoxysilyl)ethane; 1,2-bis(triethoxysilyl)ethane; 1,2-bis(methyldiethoxysilane) 1,2-bis(methyldimethoxysilyl)ethane; vinyltriethoxysilane; vinyltrimethoxysilane; mercaptopropyltrimethoxysilane; mercaptopropyltriethoxysilane; 1,2-bis(triethoxysilyl)ethylene; 1,2-bis(trimethoxysilyl)ethylene; 1,1-bis(triethoxysilyl)ethane; 1,1-bis(trimethoxysilyl)ethane; 1,4-bis(triethoxysilylethyl)benzene; 1,4-bis(trimethoxysilylethyl)benzene; 1,3-bis(triethoxysilylethyl)benzene; or 1,3-bis(trimethoxysilylethyl)benzene, octadecyltrimethoxysilane, octadecyltriethoxysilane, octyltrimethoxysilane, octyltriethoxysilane, dodecyltrimethoxysilane, and dodecyltriethoxysilane.

[0274] In some other such embodiments, the alkoxysilane used is tetraethoxysilane, and the organoalkoxysilane used is octadecyltrimethoxysilane.

[0275] In some such embodiments, the alkoxysilane, one or more organoalkoxysilanes, or combinations thereof are pre-diluted with ethanol.

[0276] In some such embodiments, a pre-diluted ethanol solution of an alkoxysilane, one or more organoalkoxysilanes, or a combination thereof is added at a slow and constant rate to prevent the formation, aggregation, and agglomeration of fine particles.

[0277] In other such embodiments, a pre-diluted ethanol solution of an alkoxysilane, one or more organoalkoxysilanes, or a combination thereof is added at a rate between 5 µL / min and 500 µL / min.

[0278] In some implementations, a second solution containing ethanol, water, and ammonium hydroxide is added at a slow and constant rate to prevent the generation, aggregation, and agglomeration of fine particles.

[0279] In some other embodiments, a second solution comprising ethanol, water, and ammonium hydroxide is placed in a particle surface area (m²) that maintains a uniform ratio. 2 The rate required to maintain a uniform ratio of particle volume (m) to the reaction volume. 3 Add within the range between the required rate and the reaction volume.

[0280] In some embodiments, porosity is introduced by one or more of the following methods through extraction, degradation, hydrolysis, deprotection, or transformation of hybrid groups: extraction with acid, water, or organic solvents; ozone decomposition treatment; heat treatment at <500°C or between 500°C and 1000°C.

[0281] In other embodiments, porosity is introduced by a combination of acid extraction, ozone decomposition treatment and / or heat treatment at <500°C, through extraction, degradation, hydrolysis, deprotection or transformation of hybrid groups.

[0282] In some implementations, the individual layers are applied using a mixture of formula XX. (D) d (E) e (F) f (Formula XX) in, a) d+e+f=1 b) D is one or more inorganic components at the initial condensation. c) E is one or more hybrid components at the initial condensation. d) F is one or more hybrid components during the initial condensation, which can further react to increase the porosity of the surface porous layer.

[0283] In some such embodiments, the precursor of the inorganic component (D) at the initial condensation is selected from oxides, hydroxides, ethoxides, methanols, propoxides, isopropoxides, butoxides, sec-butoxides, tert-butoxides, isobutoxides, phenoxides, ethylhexanols, 2-methyl-2-butanols, nonanols, isooctanools, glycolates, carboxylates, nitrates, chlorides, and mixtures thereof.

[0284] In other such embodiments, the precursor of the inorganic component (D) during initial condensation is selected from tetraethoxysilane, tetramethoxysilane, triisopropoxide methyl titanium, triphenol methyl titanium, allyl acetoacetate triisopropoxide titanium, triisopropoxide methacrylate, methacryloyloxyethyl acetoacetate triisopropoxide titanium, pentamethylcyclopentadienyl trimethoxy titanium, pentamethylcyclopentadienyl trichloride titanium, and methacryloyloxyethyl acetoacetate tri-n-propoxide zirconium.

[0285] In other such embodiments, the precursor of the hybrid component (E) during initial condensation is selected from 1,2-bis(triethoxysilyl)ethane, 1,2-bis(trimethoxysilyl)ethane, 1,4-bis(triethoxysilyl)benzene, 1,4-bis(trimethoxysilyl)benzene, 1,3-bis(triethoxysilyl)benzene, 1,3-bis(trimethoxysilyl)benzene, 1,3,5-tri(triethoxysilyl)benzene, 1,3,5-tri(trimethoxysilyl)benzene, and bis(4-triethoxysilylphenyl)diethoxysilane.

[0286] In other such embodiments, the precursor of the hybrid component (F) during the initial condensation, which may be further reacted to increase the porosity of the surface porous layer, is selected from phenyltrimethoxysilane, phenyltriethoxysilane, acetoxyethyltrimethoxysilane; acetoxyethyltriethoxysilane; chloroethyltriethoxysilane; chloroethyltrimethoxysilane; methacryloxypropyltrimethoxysilane; methacryloxypropyltriethoxysilane; bromoethyltrimethoxysilane; bromoethyltriethoxysilane; fluorotriethoxysilane; fluorotrimethoxysilane; and alkoxysilanes of the following types: (CH3CH2O) 4-v Si(OR*) v (Formula XXb) in R * For the corresponding octadecyl, dodecyl, octyl, 2-ethoxyethyl, or 3-ethyl-3-pentyl groups, V is an integer equal to 1 to 4.

[0287] In such implementations, porosity is introduced by reacting the hybrid group F through desilylation, hydrolysis, deprotection, acid extraction, heat treatment <500°C, oxidation, ozone decomposition, or decomposition.

[0288] Another aspect of the invention provides a method for generating a material with increased hybrid content near the surface of a material by modifying a silica core using one or more layers formed by organosiloxanes, mixtures of organosiloxanes and alkoxysilanes, polyorganoalkoxysilanes, hybrid inorganic / organic surrounding materials, or combinations thereof.

[0289] Another aspect of the present invention provides a method for generating a surface porous hybrid material with increased hybrid content near the outer surface of a material by modifying the surface porous material using one or more layers formed by organosiloxanes, mixtures of organosiloxanes and alkoxysilanes, polyorganoalkoxysilanes, hybrid inorganic / organic surrounding materials, or combinations thereof.

[0290] Another aspect of the present invention provides a method for generating surface porous hybrid particles with increased hybrid content near the outer surface of particles by modifying the surface porous particles using one or more layers formed by organosiloxanes, mixtures of organosiloxanes and alkoxysilanes, polyorganoalkoxysilanes, hybrid inorganic / organic surrounding materials, or combinations thereof.

[0291] Another aspect of the invention provides a method for generating surface porous hybrid particles with increased hybrid content near the outer surface of particles by modifying the surface porous particles (basic silica (>90 mol%)) with one or more layers formed by organosiloxanes, mixtures of organosiloxanes and alkoxysilanes, polyorganoalkoxysilanes, hybrid inorganic / organic surrounding materials, or combinations thereof.

[0292] Another aspect of the present invention provides a method for generating surface porous hybrid particles with increased hybridization content near the outer surface of particles, comprising the following steps: a.) Formation of surface porous particles, which are essentially silica (>90 mol%) and have a density between 0.18 cm⁻¹. 3 / g to 0.50cm 3 Pore ​​volume between / g; and b.) Modifying the particles by using one or more layers formed from organosiloxanes, mixtures of organosiloxanes and alkoxysilanes, polyorganoalkoxysilanes, hybrid inorganic / organic surrounding materials, or combinations thereof, thereby reducing the porosity of the particles by 0.01 cm. 3 / g to 0.20cm 3 / g.

[0293] In some embodiments of the invention, the method provides a material in which 1 to 15 layers are formed during the process. In other aspects, 2 to 5 layers are formed. In still other aspects, 1 to 2 layers are formed.

[0294] In some embodiments of the present invention, the individual layers of the chromatographic surface material or the chromatographic material as a whole are optimized by acid extraction, fractionation, ozone decomposition, hydrothermal treatment, acid treatment or a combination thereof.

[0295] In other embodiments of the invention, the chromatographic material of the invention is further surface modified. In some aspects, surface modification is performed by coating a polymer; coating a polymer by a combination of organic group and silanol group modification; a combination of organic group modification and coating a polymer; a combination of silanol group modification and coating a polymer; forming organic covalent bonds between the organic groups of the material and the modifying agent; or a combination of organic group modification, silanol group modification and coating a polymer.

[0296] Optional methods for synthesis Various methods can be used to apply chromatographic surface materials to the chromatographic core or to subsequent layers of the chromatographic surface material.

[0297] The method described herein allows for the synthesis of narrow-size porous material particles with pore geometry that enhances chromatographic properties.

[0298] This method involves modifying the conventional Stöber-growth method to condense a tetraalkoxysilane (e.g., tetraethoxysilane or tetramethoxysilane) alone or co-condensed with a second organosilane. A non-limiting description of the method is provided below.

[0299] Method A: Step 1) With or without a surfactant or pore-structuring agent (including pore-expanding molecules and polymers), the tetraalkoxysilane is subjected to (R...) 1 ) a (R 2 ) b (R 3 ) c Si(OR 4 ) d Condensation occurs under certain conditions to form seed particles (0.2µm to 10µm).

[0300] Step 2) In the presence or absence of surfactants or pore-structuring agents (including pore-expanding molecules and polymers), in the presence or absence of (R) 1 ) a (R 2 ) b (R 3 ) c Si(OR 4 ) d In this case, seed particles are grown by condensing tetraalkoxysilane to form larger core particles (0.3µm to 20µm).

[0301] Step 3) With or without surfactants or pore-structuring agents (including pore-expanding molecules and polymers), by reacting tetraalkoxysilane with (R 1 ) a (R 2 ) b (R 3 ) c Si(OR 4 ) d Co-condensation allows the particles to grow further to obtain non-porous particles (0.4µm to 20µm).

[0302] Step 4) Improve particle size distribution through particle classification technology.

[0303] Step 5) Porous silica particles are produced by removing organic groups and / or surfactants through heat treatment.

[0304] Step 6) Use fluorinated chemical techniques, including ammonium difluoride and hydrofluoric acid, to modify the pore structure.

[0305] Step 7) Modify the pore structure by hydrothermal treatment, with or without surfactants or pore-structuring agents (including pore-expanding molecules and polymers).

[0306] Step 8) Improve particle size distribution through particle classification technology.

[0307] Step 9) Use high temperature treatment (>600℃) to improve the mechanical stability of the particles.

[0308] Step 10) Prepare the particulate surface for modification by acid treatment (e.g., hydrochloric acid or hydrofluoric acid).

[0309] Step 11) Chemical modification of the particle surface.

[0310] Method B: Step 1) With or without a surfactant or pore-structuring agent, the tetraalkoxysilane is subjected to (R...) 1 ) a (R 2 ) b (R 3 ) c Si(OR 4 ) d Condensation occurs under certain conditions to form seed particles (0.2µm to 10µm).

[0311] Step 2) With or without surfactants or pore-structuring agents, with or without (R 1 ) a (R 2 ) b (R 3 ) c Si(OR 4 ) d In this case, seed particles are grown by condensing tetraalkoxysilane to form larger core particles (0.3µm to 20µm).

[0312] Step 3) With or without surfactants or pore-structuring agents (including pore-expanding molecules and polymers), by reacting tetraalkoxysilane with (R 1 ) a (R 2 ) b (R 3 ) c Si(OR 4 )d Co-condensation allows the particles to grow further to obtain non-porous particles (0.4µm to 20µm).

[0313] Step 4) Improve particle size distribution through particle classification technology.

[0314] Step 5) Remove organic groups and / or surfactants by heat treatment or extraction techniques to produce porous silica particles.

[0315] Step 6) Use fluorinated chemical techniques, including ammonium difluoride and hydrofluoric acid, to modify the pore structure.

[0316] Step 7) In the presence of surfactants and / or pore-structuring agents (including pore-expanding molecules and polymers), pore structure modification is performed by pseudomorphic transformation.

[0317] Step 8) Remove surfactants by extraction or by calcination.

[0318] Step 9) Modify the pore structure by hydrothermal treatment, with or without surfactants or pore-structuring agents (including pore-expanding molecules and polymers).

[0319] Step 10) Improve particle size distribution through particle classification technology.

[0320] Step 11) Use high temperature treatment (>600℃) to improve particle mechanical stability.

[0321] Step 12) Prepare the particulate surface for modification by acid treatment (e.g., hydrochloric acid or hydrofluoric acid).

[0322] Step 13) Chemical modification of the particle surface.

[0323] Method C (a specific form of Method A): Step 1) condense Si(OCH2CH3)4 to form seed particles (0.2µm to 2µm).

[0324] Step 2) Seed particles are grown by condensation of Si(OCH2CH3)4 to form larger core particles (0.3µm to 7µm).

[0325] Step 3) With or without a pore-structuring agent (e.g., mesitylene or an alkane), the particles are further grown by co-condensation of Si(OCH2CH3)4 with RSi(OR')3 (R = octyl or octadecyl, and R' is methyl or ethyl) to obtain non-porous particles (0.4 µm to 10 µm). Here, R = octyl or octadecyl, and R' is methyl or ethyl.

[0326] Step 4) Improve particle size distribution through particle classification technology.

[0327] Step 5) Organic groups are removed by heat treatment (500°C to 600°C in air) to produce porous silica particles.

[0328] Step 6) Modify the pore structure using ammonium difluoride (4 to 20 hours, 25°C to 60°C).

[0329] Step 7) Modify the pore structure by hydrothermal treatment (7 to 20 hours, pH 5-7, 90°C to 150°C).

[0330] Step 8) Improve particle size distribution through particle classification technology.

[0331] Step 9) Use high temperature treatment (800°C to 10,000°C) to improve particle mechanical stability.

[0332] Step 10) Use hydrofluoric acid treatment to prepare the particulate surface for modification.

[0333] Step 11) Chemically modify the particle surface using a chlorosilane coupling and end-capping scheme.

[0334] Method D (Modified Core Particles): Step 1) Activate the surface of <10µm particles (e.g., diamond, zirconium oxide, titanium dioxide, iron oxide, cerium, cobalt, cobalt oxide, carbon, silicon dioxide, silicon carbide) by using acid, alkali, chemical reduction, chemical oxidation treatment, or by connecting with surface modification groups (e.g., amine, surfactant, silane bond adsorption).

[0335] Step 2) In the presence or absence of surfactants or pore-structuring agents (including pore-expanding molecules and polymers), in the presence or absence of (R) 1 ) a (R 2 ) b (R 3 ) c Si(OR 4 ) d In this case, particle growth is achieved by condensing tetraalkoxysilane.

[0336] Step 3) With or without surfactants or pore-structuring agents (including pore-expanding molecules and polymers), by reacting tetraalkoxysilane with (R 1 ) a (R 2 ) b (R 3 ) c Si(OR 4 ) d Co-condensation allows the particles to grow further, resulting in non-porous particles.

[0337] Step 4) Improve particle size distribution through particle classification technology.

[0338] Step 5) Remove organic groups and / or surfactants by heat treatment or extraction techniques to produce porous silica particles.

[0339] Step 6) Use fluorinated chemical techniques, including ammonium difluoride and hydrofluoric acid, to modify the pore structure.

[0340] Step 7) In the presence of surfactants and / or pore-structuring agents (including pore-expanding molecules and polymers), pore structure modification is performed by pseudomorphic transformation.

[0341] Step 8) Remove surfactants by extraction or by calcination.

[0342] Step 9) Modify the pore structure by hydrothermal treatment, with or without surfactants or pore-structuring agents (including pore-expanding molecules and polymers).

[0343] Step 10) Improve particle size distribution through particle classification technology.

[0344] Step 11) Use high temperature treatment (>600℃) to improve particle mechanical stability.

[0345] Step 12) Prepare the particulate surface for modification by acid treatment (e.g., hydrochloric acid or hydrofluoric acid).

[0346] Step 13) Chemical modification of the particle surface.

[0347] method AD Alternative solutions Several alternatives within method AD can be explored. For example, if the particles are substantially uniform in size after growth, further sizing may not be necessary. Other steps that can be avoided include modification with fluorinated chemicals prior to pseudomorphic transformation; or, if the particles already possess sufficient mechanical strength without this step, using higher temperature treatments to improve particle mechanical stability.

[0348] Method D can be used to prepare porous magnetic particles.

[0349] In-tank, online, or offline magnetic capture methods As described in this paper, both the AMT and University College Cork methods require post-processing in a repeated process of centrifugation during the formation of the porous surface layer, followed by redispersion. Problems with repeated centrifugation include aggregation / agglomeration, difficulty in redispersing particles, product uniformity, and the long labor time required for this method. Agglomeration and agglomeration are extremely detrimental to this method. In both methods, it is possible for aggregates / agglomerates to be further coated. By its very nature, repeated centrifugation allows these unaged “green” materials to come close together. Excessive centrifugation time and g-forces can result in a dense bed structure that may be difficult to redisperse. Filtration (including tangential filtration) is an alternative form of centrifugation, which allows for the formation of a less dense bed. Unfortunately, filtration may require excessively long time periods for <3µm materials carrying submicron fine particles. These submicron fine particles may easily clog the filter material, preventing complete filtration from occurring.

[0350] Several methods exist for redispersing particles, including ultrasonic baths, in-line ultrasonic generators, in-tank ultrasonic generators, acoustic horns, rotor-stator mixers, grinding, and low-shear and high-shear mixing (e.g., serrated impellers). Optimization of amplitude, frequency, and pulse sequence is used for optimal ultrasonic treatment. Adjusting conductivity, pH, and surfactant mixtures can also be used for optimal particle redispersibility (by solvent washing or controlled sequential addition of reagents). One problem with these redispersibility methods is the potential damage to the porous surface layer. The anticipated increased shear can lead to fracturing of the porous layer. The resulting material may have bare spots or a non-uniform porous layer.

[0351] Another issue is the long reaction times required for reproducible methods, such as those described by AMT and University College Cork. These methods can take longer than those typically used to synthesize fully porous particles, even when such materials can be prepared in the lab and in batches.

[0352] Another problem with this type of homogeneous shell process is the effect of recrystallization. Recrystallized particles (<0.5µm) can appear during the growth step. If they are not effectively removed, they will begin to grow preferentially over the larger porous layer and solid core material. At some points, the two particle distributions can overlap. After further processing steps, the end result is an overlapping mixture of surface-porous and fully porous particles. This overlapping mixture of particles is difficult to separate, quantify, or understand its impact on chromatographic performance, including chromatographic reproducibility.

[0353] Therefore, among the alternative methods, magnetic capture methods are used to collect magnetic core particles as an alternative to centrifugation or filtration. These methods include in-tank, online, or offline magnetic capture.

[0354] In-tank magnetic capture utilizes a removable magnetic rod (or alternatively, an electromagnet) housed within a removable or permanent glass sleeve or baffle. In this method, the magnetic rod is positioned within the glass sleeve during the capture time. After emptying the remaining reaction solution and adding fresh washing or reaction solvent, the magnetic rod is removed, allowing the bound magnetic core particles to redisperse. Alternatively, an external magnet is placed on the side of the reactor, allowing the magnetic core particles to be captured onto the reactor sidewall. After emptying the remaining reaction solution and adding fresh washing or reaction solvent, the external magnet is removed, allowing the bound magnetic core particles to redisperse.

[0355] The online magnetic trapping method involves pumping a reaction solution through a collection container in a recirculation loop. This collection container is placed within a magnetic holding block. Magnetic core particles are collected in this container. After emptying the remaining reaction solution and adding fresh washing or reaction solvent, the collection container is removed from the magnetic holding block, and the bound magnetic core particles are redispersed as they are pumped back into the reaction container. By using a suitably sized collection container (advantageously containing one or more flat surfaces), this method allows for good control over the surface area exposed to the magnetic field.

[0356] The offline magnetic capture method is similar to filtration in that the reaction solution is transferred to a second container. In this second container, a magnetic field is applied to allow controlled collection of the magnetic core particles. The reaction solution or washing solvent is removed by filtration, decanting, or siphoning. The magnetic core particles are then redispersed in a suitable solvent and transferred back to the reaction container.

[0357] During the magnetic trapping step in all these methods, loosely collected magnetic core particles are formed. These collected core particles are less dense than the cake formed by excessive centrifugation. Therefore, these particles are easily redispersed. The redispersing of the magnetic core particles is similar to the methods described above.

[0358] In this method, a non-porous magnetic core is used instead of a non-porous silica or hybrid core. The magnetic core may comprise (but is not limited to) iron oxide, iron, metal oxides, chromium dioxide, ferrite, or cobalt in a magnetic form. Advantageously, the magnetic core comprises magnetite or maghemite. The magnetic core may be present as a pure metal or metal oxide, or in combination with a second material including (but not limited to) silica, hybrids, polymers, or non-magnetic materials. For example, the magnetic core may be formed by introducing <100 nm magnetite or cobalt nanoparticles within non-porous silica or polymer particles. The magnetic nanoparticles may be uniformly dispersed nanoparticles or uniformly dispersed clusters of nanoparticles within the material, adsorbed only on its surface, or contained only within the interior of the non-porous core particles. Alternatively, 0.3 µm to 1.5 µm magnetite or cobalt particles may be used as the non-porous core. Magnetic trapping methods are used in this method instead of centrifugation or filtration.

[0359] To reduce unwanted chromatographic interactions attributable to the core, a non-porous surface coated with silica, a hybrid, or a polymer composition can be advantageously used. This surface coating step can advantageously be repeated or performed during growth to achieve the desired thickness. Magnetic trapping methods are used in place of centrifugation or filtration during this process. To ensure that the core morphology remains substantially unchanged, this step advantageously provides a uniform surface layer. Calcination and surface re-hydroxylation can advantageously be utilized at the end of this step.

[0360] A uniform silica or hybrid surface porous layer can be formed by any of the methods described above. To ensure that the core morphology remains substantially unchanged, this step advantageously yields a highly uniform porous layer. Magnetic trapping methods are used in this process instead of centrifugation or filtration. Subsequently, additional steps such as grading, calcination, pore modification, recalcination, rehydroxylation, and bonding are performed (as needed), as detailed above.

[0361] Considering the issues associated with recrystallized particles in uniform layer methods (such as the novel one mentioned above) or the University of Cork method, magnetic core particles allow for a unique way of separating porous layer materials from recrystallized particles. This can be used during the process or during post-processing of the product.

[0362] The use of magnetic core particles and magnetic trapping methods allows for the automated synthesis of a unique process for porous surface particles. The use of in-vessel magnetic trapping (e.g., using electromagnets) enables fully automated particle collection. Automatic bottom valves and solvent addition valves are used for fully automated synthesis conditions. In-vessel or online particle size measurement is used to monitor reaction performance and determine reaction completion.

[0363] Separation equipment and housing On the other hand, various separation devices are provided, which have a stationary phase comprising materials as described herein. These separation devices include, for example, chromatographic columns, thin-layer plates, filter membranes, sample purification devices, and microtiter plates; packing materials for HPLC columns; solid-phase extraction (SPE); ion exchange chromatography; magnetic bead applications; affinity chromatography and SPE adsorbents; chelating agents; solid supports for combinatorial chemistry; solid supports for the synthesis of oligosaccharides, peptides, and / or oligonucleotides; solid-loaded bioassays; capillary bioassay devices for mass spectrometry; templates for controlled macroporous polymer membranes; capillary chromatography; electric pump packing materials; packing materials for microfluidic devices; polymer additives; catalyst supports; and packing materials for microchip separation devices. Similarly, the materials of the present invention can be packed into preparative, microporous, capillary, and microfluidic devices.

[0364] The materials of this invention impart improved lifespan to these devices due to their improved stability. Therefore, in a particular aspect, this invention provides a chromatographic column with improved lifespan, comprising: a) A column with a cylindrical interior for receiving filling material, and b) A packed chromatography bed containing the materials described herein.

[0365] In another particular aspect, the present invention provides a chromatographic apparatus comprising: a) Internal channels for receiving filling material, and b) A packed chromatography bed containing the materials described herein.

[0366] The present invention also provides a kit comprising the materials as described herein and an instruction manual. In one embodiment, the instruction manual is intended for use with separation equipment such as chromatographic columns, thin-layer plates, filter membranes, sample purification devices, solid-phase extraction devices, microfluidic devices, and microtiter plates.

[0367] The chromatographic materials of this invention can be used in a variety of chromatographic separation methods. Therefore, the equipment and kits can be used in such methods. Examples of chromatographic separation methods in which the materials of this invention can be used include, but are not limited to, HPLC separation, normal-phase separation, reversed-phase separation, chiral separation, HILIC separation, SFC separation, affinity separation, perfusion separation, partial perfusion separation, and SEC separation. Example

[0368] The invention can be further illustrated by describing the following non-limiting examples of chromatographic materials.

[0369] Material Unless otherwise specified, all reagents shall be used as is. Those skilled in the art will recognize the following supplies and equivalents of the suppliers, and therefore the suppliers listed below should not be construed as restrictive.

[0370] Characterization Those skilled in the art will recognize the existence of the following instruments and their suppliers' equivalents, and therefore the instruments listed below should not be construed as restrictive.

[0371] %C, %H, and %N values ​​were measured by combustion analysis (CE-440 elemental analyzer; Exeter Analytical Inc., NorthChelmsford, MA), or %C was measured by coulometric carbon analyzer (module CM5300, CM5014, UIC Inc., Joliet, IL). Specific surface area (SSA), specific pore volume (SPV), and average pore size (APD) of these materials were measured using the multi-point N2 adsorption method (Micromeritics ASAP 2400: Micromeritics Instruments Inc., Norcross, GA). SSA was calculated using the BET method, SPV was a single-point value measured for P / P0 > 0.98, and APD was calculated from the adsorption isotherm log using the BJH method. Median mesopore diameter (MPD) and mesopore volume (MPV) were measured by mercury porosimetry (Micromeritics AutoPore IV, Micromeritics, Norcross, GA). Scanning electron microscopy (SEM) image analysis was performed at 7 kV (JEOL JSM-5600 instrument, Tokyo, Japan). Focused ion beam scanning electron microscopy (FIB / SEM) image analysis was performed by Analytical Answers Inc. (Woburn, MA) on a FEI Model 200 focused ion beam instrument and a Hitachi S4800 Ultra-field emission SEM. Particle size was measured using a Beckman Coulter Multisizer 3 analyzer (30 µm orifice, 70,000 counts; Miami, FL). Particle size (dp) was determined as the 50% cumulative diameter of the volumetric particle size distribution. Distribution width was determined as the 90% cumulative volume diameter divided by the 10% cumulative volume diameter (expressed as a 90 / 10 ratio). Light scattering particle size was measured in water using a Malvern Mastersizer 2000. Particle size and zeta potential of nanoparticles were measured using a Malvern ZetaSizer NanoSeries (ZEN3600 model). Multinuclear (MP) samples were obtained using a Bruker Instruments Avance-300 spectrometer (7mm dual broadband probe). 13 C, 29 Si)CP-MAS NMR spectroscopy. Rotation speeds were typically 5.0 kHz to 6.5 kHz, with a cycle delay of 5 seconds and a cross-polarized contact time of 6 milliseconds. External standard adamantane ( 13 (C CP-MAS NMR, δ 38.55) and hexamethylcyclotrisiloxane ( 29Si CP-MAS NMR (δ -9.62), compared to the tetramethylsilane recording reported. 13 C and 29 Si CP-MAS NMR spectral shifts. Populations in different silicon environments were evaluated using DMFit software via spectral deconvolution. [Massiot, D.; Fayon, F.; Capron, M.; King, I.; Le Calvé, S.; Alonso, B.; Durand, J.-O.; Bujoli, B.; Gan, Z.; Hoatson, G. Magn. Reson. Chem. 2002, 40, 70-76]. Grading techniques are described, for example, by W. Gerhartz et al. (editors). Ullmann's Encyclopedia of Industrial Chemistry 5th Edition, Volume B2: Unit Operations I, VCHVerlagsgesellschaft mbH, (Weinheim, Fed. Rep. Germ. 1988). Magnetic measurements were performed using a vibrating sample magnetometer (ADE / DMS type 880) by ArKival Technology Corporation (Nashua. NH). Phase characterization was performed by wide-angle X-ray powder diffraction (XRPD) analysis (H&M Analytical Services, Inc. Allentown. NJ) using a Bruker D4 diffractometer (Cu radiation, 40 kV / 30 mA). Scans were performed in the angular range of 10° to 90°2-θ with a step size of 0.02° and a counting time of 715 seconds per step.

[0372] Example 1 Make the surface porous silica layer (Scheme 1, Figure 28 ) is formed on a non-porous silica core material, which is obtained through Stöber (US 3,634,558; J. Coll. Interf. Sci. The general method of , 1968, 26, 62, using Wyndham (US20130112605, US 20130206665), Kirkland (US 20070189944; 20080277346), Blue ( J. Chromatogr. A , 2011, 1218 (44), 7989) and Brennan ( J. Mater. Chem.The polymer electrolyte layering method described in [2012, 22, 13197] prepares the product. In this method, porous layers are formed by alternately adding polymer electrolytes and silica nanoparticles (or silica sol) (Muriithi, BW PhD dissertation, University of Arizona, 2009, p. 396) in a layer-by-layer manner. In this method, only nanoparticles of a single size are used for each prototype.

[0373] As detailed in Wyndham (US 20130112605, US 20130206665), the polymeric electrolyte was removed by heat treatment in air at temperatures greater than 500°C to 600°C for 10 to 20 hours. To further strengthen these materials, a second heat treatment at 825°C to 1000°C for 10 to 20 hours was performed. The rehydroxylation step was carried out using the method described in Example 64 of Wyndham (US 20130112605, US 20130206665). Table 1 contains the relevant synthetic parameters and characterization data. Core diameter was determined digitally using a Coulter counter. Nanoparticle size was determined using a Zetasizer, and SEM was used to confirm the nanoparticle size used in product 1n-1r. Rho was estimated from the SEM data. For the ultrathin shell products (1m and 1p), some error was noted in this calculation, which was estimated by this method to be greater than 1. For products 1j and 1n, MPD (131 Å, 308 Å) and MPV (0.28 cm⁻¹) were measured by mercury porosimetry. 3 / g, 0.09cm 3 / g) (shown in parentheses respectively).

[0374] Table 1 To better understand the influence of pore structure in porous materials, we examine the variation of physical properties across the particle distribution function radius. This distribution method allows relevant points (including molecules, atoms, and particles) to be represented as a function of distance from the center point. Such techniques have been used to evaluate the distribution of chromatographic particles in packed beds (Bruns, SJ Chromatogr. A, 2012, 1268, 53). Where tools such as image analysis or computational simulations are typically used to estimate distribution or ordination, here we employ a simpler visual representation of this method when applied to porous media to understand the variation of pore surface area and pore size from the center point.

[0375] Figure 1 This displays the cross-sectional geometry of porous and surface-porous particles. The key parameter for surface-porous particles is defined as the particle center (…). cCore diameter ( d ), particle size ( d’ or 2 l ), particle radius ( l The porous layer consists of a core diameter (0) at the radial starting point and a porous layer terminal (1) at the radial ending point. The ratio of the core diameter to the particle diameter (denoted as Rho) is defined as d / d'. In the absence of a porous layer, Rho is 1.

[0376] The key parameter of fully porous particles is the particle center ( c ), particle size (d' or 2) l ), particle radius ( l The Rho of a fully porous particle is defined as follows: the center of the porous particle (0=c), and the terminal of the porous particle along its radius. In the absence of a core particle, the Rho of a fully porous particle is 0.

[0377] Figure 2 The expected surface area and pore size distribution along the radius is shown. All parameters are normalized from the low state (0) to the maximum value (1). The solid line represents the planned change in surface area and pore size from the non-porous particle core to the outer particle surface. The dashed line represents the expected deviation from this line at the core surface and near the starting point of the porous layer. In contrast, fully porous materials are expected to have uniform pore size and surface area from the material center to the surface.

[0378] Another important parameter is the final particle size. With regard to fully porous particles, columns containing smaller particles (e.g., <2µm in diameter) are expected to yield higher column efficiency and peak capacity when used in gradient separations when employed in a properly constructed liquid chromatography system.

[0379] It is known in the art that an Rho concentration of 0.6–0.8 is preferred for surface porous particles used in the chromatographic separation of smaller molecules. An Rho concentration of 0.8–0.95 is preferred for surface porous materials used in the chromatographic separation of larger molecules (K. Horváth, J. Chromatogr. A , 2010, 1217 (41), 6373; G. Guiochon, J. Chromatogr. A , 2011, 1218 (15), 1915).

[0380] Another important parameter is the average pore size (APD). A pore size between 70 Å and 130 Å is preferred for the separation of small molecules and smaller biomolecules. When the APD is less than 70 Å, the resulting material typically consists of micropores with increased volume. When the APD is greater than 130 Å, the resulting column is expected to exhibit significant column ratio, retention, and capacity loss. The column ratio (β) is defined as shown in Equation 1 (ε = interstitial porosity; p = skeletal density of the stationary phase).

[0381] β=(1-ε) • SSA / (SPV + (ε / p)) Formula 1 Materials with an APD greater than 120 Å are preferred for the separation of larger molecules and biomolecules. For various reversed-phase separations of peptides and smaller proteins, a pore size of 120 Å to 200 Å is preferred. For the reversed-phase separation of many larger proteins, a pore size between 150 Å and 450 Å is preferred. It may be preferable that even larger biomolecules such as vaccines, viruses, antibody-drug-conjugates, larger oligonucleotides and RNA, and the separation of virus-like particles may require an APD between 300 Å and 900 Å. For ion-exchange separations of larger biomolecules, the use of non-porous materials (e.g., Rho=1) may be preferred. The problem with using columns containing materials with smaller APDs is the exclusion of larger molecules. However, if the APD is excessive for the separation of a given macromolecule, the same problems arise regarding retention and column-to-column loss.

[0382] The average pore size (APD) of surface porous materials can be controlled by carefully selecting the nanoparticle size of the sol used in the layer-by-layer method. The effect of nanoparticle size on surface area and pore size can be roughly estimated using the following formula 2-4.

[0383] SSA 纳米粒子 = 6,000 / {dp 纳米粒子 • p 纳米粒子} Formula 2 SSA 表面多孔颗粒 = w 芯 •SSA 芯 + (1- w 芯 SSA 纳米粒子 Formula 3 APD = 40,000 SPV 表面多孔颗粒 / SSA 表面多孔颗粒 Formula 4 like Figure 3 As shown, the estimated surface area (SSA) of these nanoparticles decreases significantly with increasing nanoparticle size. When these different nanoparticles are subsequently used to synthesize surface porous materials, they exhibit varying surface areas. For the resulting surface porous products, larger nanoparticles lead to lower SSA and larger surface area (APD).

[0384] Figure 4 The core material weight fraction is estimated as Rho changes, and Figure 5 Estimated surface areas of porous materials with different surface sizes prepared using varying nanoparticle sizes were plotted. When following the... Figure 3A similar trend is observed, with the surface porous material's surface salinity (SSA) decreasing further due to the presence of the core material. For different materials, a thinner porous layer thickness (e.g., a higher Rho) also leads to a lower SSA. A change in Rho of 0.70 to 0.90 is expected to cause the surface porous material's SSA to decrease by a factor of two.

[0385] like Figure 5 and Figure 6 As detailed, the SSA obtained from surface porous products is estimated for materials prepared using different nanoparticle sizes. For example... Figure 7 As shown, materials prepared with different nanoparticle sizes are expected to have different APDs for the products. For different Rho materials prepared with a given nanoparticle size, no major difference in APD relative to Rho is expected for Rho values ​​smaller than approximately 0.95 (e.g., 0 <= Rho <= 0.95). This is understood as shown in Equation 4, where SPV and SSA have an inverse relationship. As Rho decreases, SSA (m 2 / g) and SPV (cm 2 The ratio ( / g) increases. When a uniform porous layer is formed without porosity change, such a result is expected to result in a constant APD relative to Rho. Although not theoretically limited, an exception is when the initial layer is formed on the core surface, for higher Rho. For higher Rho materials, there may be a larger porosity change during the formation of the initial porous layer, leading to differences in APD.

[0386] Using Equations 2-4, we can estimate the apparent nanoparticle size of the products in Table 1. For products 1a-1h fed with 11 nm nanoparticles, we determined the average apparent silica nanoparticle size of the final product to be 11.4 nm. For products 1i-1j fed with 20 nm nanoparticles, we determined the average apparent silica nanoparticle size to be 17.7 nm. Figure 8 SSA data for products 1a-1j are included along with modeled SSA data. Although not limited by theory, it should be understood that the differences in nanoparticle size can be attributed to analytical techniques and calculations, necking between nanoparticles within the porous layer (e.g., increased coordination number of the porous network), differences in pore structure due to mild maturation from exposure to water, and / or differences in porous layer modification during heat treatment (e.g., viscous sintering).

[0387] When prepared using nanoparticles of the same size, with apparent dp 纳米粒子 A general trend exists in the final products with higher Rho sizes. For example, when observing products formed from 11 nm nanoparticles (1a-1h), lower Rho materials (products 1a-1d) show a greater apparent dp. 纳米粒子The size (10 nm to 11 nm) showed good consistency with the size of the nanoparticles used in the method. Higher Rho materials prepared using the same 11 nm nanoparticles (products 1f-1h) exhibited higher dp. 纳米粒子 Size (14nm to 22nm). By examining the precursor of 1g of the final heat-treated product, we determined the dp to be 17nm. 纳米粒子 Size. This better matches other higher Rho materials. 1g of product exhibits a 20% surface area loss during the final heat treatment step. This indicates that thinner shell materials (higher Rho) can deviate from the model detailed above. These deviations are... Figure 2 The model indicates the trend as a dashed line.

[0388] Example 2 Another method for modifying porous materials for porous media is hydrothermal treatment. Pore maturation methods, which lead to a decrease in SSA and an increase in APD, can be employed by exposing the porous material to elevated temperatures and pH, as described by Jiang {US 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008 / 103423}. In this method, the general method of Example 1 is modified to include hydrothermal treatment (20 hours) prior to the final heat treatment, using the general method detailed by Jiang (US 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008 / 103423}. For a method overview, see Scheme 2. Figure 28 .

[0389] Table 2 contains the relevant synthesis parameters and characterization data. Precursors for products 2a-2p were prepared using 11 nm silica nanoparticles. Precursors for products 2q-2r were prepared using 20 nm silica nanoparticles. The Rho values ​​for these products, except for products 2n-2o (Rho = 0.86) and 2p (Rho = 0.93), ranged from 0.70 to 0.73. Column ratios (β) were calculated using Equation 1. The final product ratios (SSAf / SSAi.) and pore size ratios (APDf / APDi) were calculated for products 2a-2f and after hydrothermal treatment of products 2g-2m. Products 2a-2h, under mild hydrothermal conditions, exhibited a moderately increased apparent nanoparticle size. More demanding conditions, such as higher temperatures (products 2i, 2k-2p) and higher pH (products 2i-2r), showed a significant decrease in SSA, an increase in APD, and an increase in apparent silica nanoparticle size.

[0390] As described in Example 1, for materials prepared using a single type of nanoparticle, no significant changes in porosity, surface area, or pore size across the porous layer were expected. While not bound by theory, it should be understood that because nanoparticles of a single size are used, the material is homogeneous from the core surface to the outer surface prior to hydrothermal treatment. The expected result of hydrothermal treatment is a uniform increase in pore size and a decrease in surface area.

[0391] Products 2a-2h exhibited similar Rho and were prepared using nanoparticles of similar size. Hydrothermal treatment was performed at the same temperature (1000℃) using different pH conditions (pH 4-8). As pH increased, we observed a general trend in the data: SSA decreased (115m). 2 / g-85m 2 / g), APD increases (110Å-144Å). β Reduce (133m) 2 / cm 3 -101m 2 / cm 3 ), SSAf / SSAi Decrease (0.84-0.50), APDf / APDi Increase (1.00-1.72), and apparent dp 纳米粒子 Size increased (11.-14nm).

[0392] The product 2j-2m has a similar Rho and was prepared using nanoparticles of similar size. Hydrothermal treatment was performed at different temperature conditions (100℃-155℃) at the same pH (0.3M Tris, pH 9.8). As the temperature increased, we observed a general trend in the data: SSA decreased (70m). 2 / g-34m 2 / g), APD increases (108Å-334Å). β Reduce (110m) 2 / cm 3 -43m 2 / cm 3 ), SSAf / SSAi Decrease (0.83-0.29). APDf / APDi Increased (1.16-3.12), and apparent dp 纳米粒子 Size increases (17nm-36nm). Similar trends were also observed in products 2f and 2i, as well as products 2q and 2r, with increasing temperature.

[0393] Products 2n-2p were prepared using nanoparticles of similar size. Hydrothermal treatment was performed at the same pH (0.2 M Tris, pH 80) and temperature conditions (160 °C). For these products, Rho varied from 0.86 to 0.93. As Rho increased, we observed a general trend in the data: SSA decreased (15 m 2 / g-7m 2 / g), SPV decreased (0.12cm) 3 / g-0.04cm 3 / g), and β Reduce (30m) 2 / cm 3 -19m 2 / cm 3 ).

[0394] The observed differences are not solely due to hydrothermal treatment, but also because higher Rho materials are expected to have lower SSA, SPV, and β Although changes in Rho are not expected to have a significant effect on APD, as in Example 1 and Figure 2 However, this parameter deviates for materials with higher Rho values. To further investigate, we need to comment on the variations in SSA and APD relative to the precursor materials. Because these products have the same nanoparticle size and the same hydrothermal conditions, we expect similar... SSAf / SSAi (0.24-0.25) and APDf / APDi (2.39-3.81) Relative change. Product 2n-2p in SSAf / SSAi The results were very consistent, but we observed that the thinnest shell of the highest Rho material was... APDf / APDi deviation.

[0395] Products 2f and 2q were subjected to hydrothermal treatment under the same conditions (0.2 M Tris, pH 8, 100 °C). Rho was similar for these products, but the nanoparticles used in the porous layers were 11 nm (product 2f) and 20 nm (product 2q). As the nanoparticle size increased, we observed a general trend in the data: SSA decreased (85 nm). 2 / g-63m 2 / g), APD increased (141Å-186Å) and β Decrease (102m) 2 / cm 3 -78m 2 / cm 3 Products 2f and 2q exist. SSAf / SSAiIncrease (0.50-0.69) and APDf / APDi Decrease (1.63-1.14). It should be understood that the larger nanoparticles used have a lower nanoparticle surface area, and such materials show less change during hydrothermal treatment under the same conditions.

[0396] The pore characteristics of product 2r were compared with those of product 1j. Both products used silica nanoparticles of the same size (20 nm) in the layering method and had the same Rho (0.70). Product 1j did not undergo a hydrothermal treatment step, while product 2r underwent hydrothermal treatment at pH 8 and 160 °C. Compared to product 2r, product 1j exhibited a higher SSA (73 nm). 2 / g vs. 43m 2 The porosity differences were observed in the product 2r (150 Å vs. 277 Å) and smaller apparent nanoparticle size (17 nm vs. 28 nm). The porosity differences were confirmed by mercury porosimetry. The MPD (131 Å, 232 Å) was larger for product 2r, while the MPV (0.28 cm⁻¹) was smaller for products 1j and 2r. 3 / g, 0.29cm 3 (similar to / g) (results shown in parentheses respectively).

[0397] The difference in pore characteristics between products 1j and 2r can be visually observed in the FIB / SEM images of the porous region. Figure 9 (As shown). These figures contain the normalized distance of the porous layers along the particle radius from 0 to 1 – as further detailed in Example 4. In this FIB / SEM comparison, it can be clearly observed that product 1j consists of smaller nanoparticles (observed as brightened spherical material in the porous region defined in these images between 0 and 1), while the hydrothermally treated product 2r consists of more interconnected spherical features. This estimate does not adequately describe the geometry of the interconnected porous layers while we can still approximate the average nanoparticle size. The image also shows the improved interconnectivity between porous layers in the non-porous core material with the hydrothermally treated product (product 2r) (observed on the left side of these images), which is expected to improve the mechanical and chemical properties of these materials. Both FIB / SEMs show similar porosity from the core to the outer surface (in the porous region defined in these images between 0 and 1) (observed as dark areas). It is important to note that a surface coating needs to be applied in the FIB / SEM analysis, which is observed as a shaded material near the outer surface of these images.

[0398] Example 3 The method of Example 1 was modified to form a porous layer (Scheme 3). Figure 28More than one type of silica nanoparticle was used. In this method, nanoparticles of different sizes were used for different steps in a layer-by-layer process of alternating addition of polymeric electrolytes and nanoparticles. Table 3 contains the relevant synthesis parameters and characterization data. Median mesopore diameter (MPD) and mesopore volume (MPV) were measured by mercury porosimetry. Silica core diameter was determined digitally using a Coulter counter. Nominal silica nanoparticle size was determined using a Zetasizer, and SEM was used to estimate the nanoparticle size of silica nanoparticles ≥20 nm. Rho was determined from SEM data, in addition to estimating the 5-day product using Coulter counter data.

[0399] The average nanoparticle size of these reactions was determined by averaging the nanoparticle size used throughout the multilayer process. For the final product, the apparent silica nanoparticle size was determined using Equations 2-4. Similar to Example 1, there was good consistency between the apparent and average nanoparticle sizes. However, this does not indicate that the nanoparticles are uniformly distributed within the porous layer.

[0400] Comparing experiments 3a-3e reveals the geometric influence of layering of nanoparticles of different sizes, thus demonstrating the effect of increasing pore size from the core surface to the material surface. Product 3a has four layers of 11 nm nanoparticles, followed by two layers of 20 nm nanoparticles – producing an SSA of 76 nm. 2 The final product has an APD of 131 Å and a g / g. Product 3b differs in its third layer by the addition of a single 99 nm nanoparticle. The final product with this 99 nm nanoparticle additional layer has a 69 nm APD. 2 / g SSA and 150Å APD. When the amount is less than 10m 2 When the SSA difference is / g, the pore size increases by 29 Å - due to the presence of larger nanoparticles in the outer layer.

[0401] Product 3c is similar to product 3a in the first six layers, but has an additional 46nm silica nanoparticle outer layer. The final product with this 46nm nanoparticle additional layer has a 77nm silica nanoparticle diameter. 2 / g SSA and 144Å APD. When this amount of product 5a is an unmeasurable change in SSA, the pore size increases by 13Å - due to the presence of larger nanoparticles in the outer layer.

[0402] Furthermore, products 3b and 3c can be compared. They share the same layering method for the first six layers, differing only in the size of the silica nanoparticles in the final outer layer. Compared to product 3c, which has smaller 46nm nanoparticles on its outer surface, product 3b, with larger 99nm nanoparticles on its outer surface, exhibits lower SSA and higher APD. Those skilled in the art will conclude from the experiments that these materials possess a larger pore size and a smaller surface area on their outer surfaces.

[0403] Product 3f has larger nanoparticles in the first four layers and smaller nanoparticles in the outer layers. It is expected that such materials will have a decreasing pore size from the core to the surface layers.

[0404] By observing product 3a ( Figure 10 ), product 3c ( Figure 11 ), product 3e ( Figure 12 ), product 3f ( Figure 14 To further understand the differences in pore size, we can analyze the nitrogen adsorption pore size characteristics (desorption, dV / dLog(D)).

[0405] The pore size distribution of product 3a, consisting of four layers of 11 nm nanoparticles followed by two layers of 20 nm nanoparticles, has shoulders for the larger pores located on the outer side of the porous shell. In contrast, product 3f, consisting of four layers of 20 nm nanoparticles followed by two layers of smaller 11 nm nanoparticles, has shoulders for the smaller pores located on the outer side of the porous layers. When compared to the pore size distribution of product 1j, which consists of six layers of 20 nm nanoparticles (… Figure 14 A more uniform aperture distribution was observed – without any significant shoulders.

[0406] The pore size distributions of products 3c and 3a also exhibit geometric differences in porosity. As detailed above, product 3a's pore size distribution has shoulders with larger pore sizes. Product 3c also forms four layers of 11 nm nanoparticles followed by two layers of 20 nm nanoparticles, but then a layer of 46 nm nanoparticles. The pore size distribution of product 3c shows a significant split, exhibiting a pore size pattern similar to that of product 3a, as well as a secondary pattern at higher pore sizes. It should be understood that as the layers progress from 11 nm, 20 nm, and 46 nm nanoparticles, the pore size gradually increases from the core material surface to the outer surface.

[0407] Changes in porosity can also be observed in product 3e ( Figure 13 ) and 3f ( Figure 15 ) were observed in FIB / SEM. Product 3e showed signs of smaller nanoparticles near the surface of the core material, and product 3f showed signs of smaller nanoparticles near the outer surface of the particles.

[0408] Example 4 We can apply a physical property distribution method to estimate the pore properties of the products selected in Examples 1 and 3. This model incorporates the effect of each layering step and is based on Equations 2-4. Using particle size data obtained from SEM, the growth of each layer can be estimated. Using the assumed constant porosity within the porous layers, the differences in surface area and pore size distribution can be plotted from the core surface (normalized distance 0) to the outer surface of the material (normalized distance 1). Figure 16 The model of product 3a is shown. Figure 17 The model of product 3e is shown. For simplicity, we remove the distance from the center (c) to the core surface (0) and exclude deviations in surface area or pore size in the region near the core surface. By considering the distribution from 0 to 1, we can better apply this model to non-spherical cores subsequently. For non-spherical cores, the core surface (0) and the material surface (1) are defined identically, and the selected distribution of physical properties along the particle radius is perpendicular (90°) to the core surface.

[0409] In this model, the averaged apparent nanoparticle sizes of Examples 1 and 3 are used. For example, the untreated products prepared using 11 nm and 20 nm silica nanoparticles have average apparent nanoparticle sizes of 11.4 nm and 17.7 nm, respectively.

[0410] Example 5 The additional materials were prepared as detailed in Example 3. Product 5a was a surface porous particle based on a 2µm non-porous silica core, using a layer of silica nanoparticles of 11nm, 20nm, 35nm, and 75nm respectively arranged in this specific order. Product 5b was a surface porous particle based on a 2µm non-porous silica core, using a layer of silica nanoparticles of 75nm, 35nm, 20nm, and 11nm respectively (arranged in this order). Product 5c was a surface porous particle based on a 2µm non-porous silica core, using three layers of 11nm silica nanoparticles, followed by three layers of 20nm silica nanoparticles, and then three layers of 11nm silica nanoparticles (arranged in this order). The Rho of products 5a-5c was 0.73. The results were modeled using the method detailed in Example 4 and are shown in... Figure 18 and Figure 19 For simplicity, we remove the distance of the x-axis from the center (c) to the core surface (0) and do not include deviations in surface area or aperture in the region near the core surface.

[0411] Example 6 By carefully selecting silica nanoparticles, novel porous materials with geometrically defined surface areas and pore sizes were generated using the methods detailed in Examples 3-5. Fully porous materials (e.g., Rho=0) can be achieved without using a pore-free core. Using this method, a variety of materials with Rho between 0.0 and 0.95 can be prepared. The selected estimated pore sizes are shown in... Figure 20 These materials are used in chromatographic separation (e.g., biomolecular separation, SEC, GPC) as well as in catalyst supports, polymer additives, fuel cells, luminescence, selective membranes, optics, optoelectronics, electronic devices, energy storage devices, sensors, and drug delivery.

[0412] Example 7 The method of the selected Example 3 was modified to include hydrothermal treatment (0.2 M TRIS, pH 8, 20 h) prior to higher temperature heat treatment, including hydrothermal treatment using the general hydrothermal treatment method detailed in Example 2. Table 4 contains the relevant synthesis parameters and characterization data. Column ratio (β) was calculated using Formula 1. Compared to the corresponding product of Example 3 without this additional hydrothermal treatment step, the final and initial surface areas of the final product (β) were compared. SSAf / SSAi ) and aperture ( APDf / APDi The ratio of ) is calculated.

[0413] Although not limited by theory, it is expected that when treated under similar conditions as in Example 2, the different layers containing nanoparticles will all be modified by hydrothermal treatment in a manner similar to that of products containing only a single nanoparticle size. The model detailed in Examples 3-4 can subsequently be modified during hydrothermal treatment to account for these expected changes in order to better predict the desired pore properties of these hydrothermally treated multilayered products. For example, product 2f was prepared using 11 nm silica nanoparticles and hydrothermally treated at 100 °C. The resulting product had a porosity of 0.50. SSAf / SSAi And 1.63 APDf / APDi The apparent nanoparticle size was 14 nm. Product 2q was prepared using 20 nm silica nanoparticles and subjected to hydrothermal treatment at 100 °C. The resulting product had a strength of 0.69. SSAf / SSAi And 1.14 APDf / APDi The apparent nanoparticle size is 19 nm. The increase in apparent nanoparticle size from 11.4 nm to 14 nm and from 17 nm to 19 nm is consistent with expectations for hydrothermal treatment under these conditions. The model modifications detailed in Examples 3-4 involve these changes in pore characteristics to better estimate the product surface properties of products 7a, 7c, 7e, and 7f. Products 7a, 7c, 7e, and 7g were all hydrothermally treated under similar conditions (100°C), and all resulted in similar SSA (60 nm). 2 / g-65m 2 / g), APD (167Å-185Å),β (76m) 2 / cm 3 -84m 2 / cm 3 ), SSAf / SSAi (0.78-0.82) and APDf / APDi (1.21-1.37) range. However, the apparent silica nanoparticle size of these products varies between 17 and 31.

[0414] Based on the results of Example 2, it is expected that the model detailed in Examples 3-4 can be modified in a similar manner to produce a material that has undergone hydrothermal treatment at 160°C. The product 2n-p was prepared using 11 nm silica nanoparticles and hydrothermally treated at 160°C. The resulting product has a strength of 0.24-0.225. SSAf / SSAi And 3.70-3.80 APDf / APDi The apparent nanoparticle size is 35nm-40nm. Product 2r was prepared using 20nm silica nanoparticles and subjected to hydrothermal treatment at 160℃. The resulting product has a strength of 0.47. SSAf / SSAi And 1.70 APDf / APDi The apparent nanoparticle size is 28 nm. While higher temperature hydrothermal treatment is expected to significantly increase the apparent nanoparticle size from 11.4 nm to 37 nm and from 17.7 nm to 28 nm, a significant increase in the smaller initial apparent nanoparticle size under these conditions is not anticipated. The model modifications detailed in Examples 3-4 have these changes in pore characteristics to better predict the product surface properties of products 7b, 7d, and 7f. Products 7b, 7d, 7f, and 7h were all hydrothermally treated under similar conditions (160°C) and all resulted in similar SSA (34 nm). 2 / g-38m 2 / g), APD (259Å-315Å), β (47m) 2 / cm 3 -54m 2 / cm 3 ), SSAf / SSAi (0.44-0.52) and APDf / APDi The apparent silica nanoparticle size of these products varies between 21 and 43. (1.92–2.40)

[0415] The improved model detailed in Examples 3-4 for estimating APD provides good agreement (5%-11% error) for the untreated products 1g, 1j, and 3a. Figure 16 ), 3f and 3e ( Figure 17 The model also provides good agreement (5%-10% error) with the actual data of the hydrothermal treated products 2q, 2r, 7a, 7e. Figure 21 ) and 7f ( Figure 22 However, it did not provide acceptable conformations for hydrothermally treated products 7b, 7g, and 7h (15%–18% error). Interestingly, further model improvements to account for one less external porous layer resulted in improved conformations for product 3f (2% error), product 7g-h (8% error), and product 7b (11% error). Considering that the product obtained from 11 nm nanoparticles during hydrothermal treatment does not contribute to APD, the model's results for product 7b (4% error) and product 7f (…) are also acceptable. Figure 23 The error calculated using the model with a 5% error rate is further reduced. Compared to the original model ( Figure 22 ), this is for product 7f ( Figure 22 The estimate is better consistent with the following FIB / SEM data.

[0416] The similarity of pore properties of materials hydrothermally treated under similar conditions does not indicate that these materials have uniform porosity from the core material surface to the outer surface of the particles. Because these materials are layered under similar conditions to the materials of Example 3 (as shown in Table 4), we expect these products to have variations in pore size and surface area distribution from the core material surface (normalized distance 0) to the outer surface of the particles (normalized distance 1).

[0417] A better understanding of the differences in pore characteristics can be obtained by examining products 7a and 7b ( Figure 10 ); products 7c and 7d ( Figure 11 ); and products 7e and 7f ( Figure 12 This is achieved by measuring the nitrogen adsorption pore size distribution (desorption, dV / dLog(D)).

[0418] The pore size distributions of products 7a and 7b can be directly compared with product 3a (without hydrothermal treatment) because these materials exhibit the same layering characteristics. As mentioned above, product 3a shows a master mold pore size greater than 100 Å, as well as shoulders with larger pore sizes (<200 Å) on the outer porous layer. Hydrothermal treatment at 100 °C results in a more uniform pore size distribution of approximately 200 Å, while hydrothermal treatment at 160 °C produces a shoulder distribution greater than 200 Å and a master mold pore size between 400 Å and 500 Å.

[0419] Similarly, the pore size distributions of products 7c and 7d can be directly compared with product 3c (without hydrothermal treatment) because these materials exhibit the same layering characteristics. As mentioned above, product 3c displays a lower pore size (greater than 100 Å) dominant mode and a higher pore size (approximately 200 Å) submode. Hydrothermal treatment at 100 °C yields a more uniform pore size distribution with a single mode pore size of approximately 200 Å. However, hydrothermal treatment at 160 °C produces a submode (greater than 200 Å) and a dominant mode between 400 Å and 500 Å.

[0420] Similarly, the pore size distributions of products 7e and 7f can be directly compared to product 3e (without hydrothermal treatment) because these materials exhibit the same layering characteristics. Product 3e, prepared with two layers of 11 nm nanoparticles followed by four layers of 20 nm nanoparticles, shows a unimodal pore size of less than 200 Å. Hydrothermal treatment at 100 °C still yields a unimodal pore size distribution, but now it is approximately 200 Å. However, hydrothermal treatment at 160 °C produces a bimodal pore size distribution, with the secondary mode approximately 200 Å and the primary mode greater than 300 Å.

[0421] Similarly, the pore size distributions of products 7g and 7h can be directly compared to product 3f (without hydrothermal treatment) because these materials exhibit the same layering characteristics. Product 3f, prepared with four layers of 20nm nanoparticles followed by two layers of 11nm nanoparticles, shows a shoulder pore size distribution greater than 100 Å and a modal pore size less than 200 Å. Hydrothermal treatment at 100°C still yields a single-mode pore size distribution, but it is now approximately less than 200 Å. Hydrothermal treatment at 160°C produces a single-mode pore size distribution with a pore size modulus less than or equal to 300 Å.

[0422] To better understand the geometric effects of hydrothermal treatment, the product 7f ( Figure 13 ), product 7g and 7h ( Figure 15 FIB / SEM was performed and compared with the relevant FIB / SEM of similar layered products formed without hydrothermal treatment (products 3e and 3f).

[0423] As described above, the pore size distribution of the untreated product (product 3e), formed by two layers of smaller nanoparticles followed by four layers of larger nanoparticles, exhibits FIB / SEM evidence of smaller nanoparticles near the core material surface. Similar layered products treated at 160°C show significantly different FIB / SEMs. The FIB / SEM of product 7f reveals erosion gaps between the core particle surface and the porous layers. These observed vacancies comprise spaces formally filled with two layers of 11 nm silica nanoparticles. While not bound by theory, it is evident that the 11 nm silica nanoparticles preferentially dissolve compared to the larger silica nanoparticles—resulting in the formation of these vacancy portions. This vacancy can be observed in the pore size distribution, with the dominant mode of product 7f greater than 300 Å. The observed submodes of product 7f below 300 Å are similar to the dominant modes observed in other products (e.g., product 7h) formed by hydrothermal treatment at 160°C using 20 nm silica nanoparticles as the primary layering material. Complete dissolution of these 11 nm silica nanoparticles was not observed in other products formed using only this type of material (e.g., product 2n-2p).

[0424] Similarly, the pore size distribution of the untreated product (product 3f), formed by four layers of larger nanoparticles followed by two layers of smaller nanoparticles, exhibits FIB / SEM characteristics showing signs of smaller nanoparticles near the outer surface. Similar layered products treated at 100°C and 160°C show different FIB / SEM characteristics. After hydrothermal treatment at 100°C, the observed change in the outer porous layer near the outer surface is present, and the observed reduction in smaller silica nanoparticles is observed. After hydrothermal treatment at 160°C, the change in the porous layer appearance via FIB / SEM is more pronounced between products 7h and 3f. The porous layer of product 7h is more open and similar to that observed in product 7f. However, unlike product 7f, there is excellent adhesion between the porous layer and the core particles. This difference in core adhesion between products 7f and 7h is due to the insolubility of smaller nanoparticles at the interface between the core and the porous layer, and the fact that the conditions for hydrothermal treatment at 160°C allow for excellent adhesion between the core and the porous layer.

[0425] The proposed model for fitting pore characteristics provides good fit for materials composed of different layered materials, both untreated and some hydrothermally treated at 100°C. However, some hydrothermally treated materials at 160°C do not follow the conventional model. Fine examination of the pore size distribution and FIB / SEM allows for a better understanding that smaller nanoparticles (e.g., 11 nm silica) may react preferentially under these conditions compared to larger nanoparticles, leading to over-erosion and opening of portions from the core particle surface to the outer surface of the particle. This is particularly true for products prepared by layering 11 nm and larger nanoparticles, where the smaller nanoparticles constitute less than approximately 33% of the layer. In unexpected cases, this preferential reaction can be utilized to generate novel pore geometries with chromatographic advantages for specific applications.

[0426] Example 8 The methods of Examples 1-7 were modified to introduce a mixture of nanoparticles within a given layer based on 1.22µm nonporous silica core particles. For example, a mixture of 11nm and 20nm silica nanoparticles (representing the weight percentage of 11-20 followed by 11nm nanoparticles). For the selected materials, hydrothermal treatment (0.2M TRIS, pH 8, 20h) was used to modify the pore structure. Table 4 contains the relevant synthesis parameters.

[0427] Table 5 Example 9 A series of proteins with similar sizes and molecular weights are shown in Table 6, derived from the references. a(J. Tencer, Kidney International , 1998, 53 (709), References b (U. Lund, Am.) J. Physiol, Renal Physiol. , 2003, 284 (F1226), and references c (EM Renkin, J. Gen. Physio. (1954, 38, 225), along with the pore size range of the porous materials used in the separation equipment for these analytes. Recommended pore sizes for porous materials used in the chromatographic analysis of molecules smaller than about 5 kDa have been reported as 60–120 Å, 200–300 Å for molecules of 5–50 kDa, and larger vaccines or proteins require larger pore sizes (1,000–4,000 Å) (www.chem.agilent.com, Agilent Document 5990-9028EN). How these recommended pore sizes are determined is not well understood; therefore, errors may exist in these recommendations. However, it should be widely understood that when 5 kDa biomolecules can be chromatographically analyzed on materials with pore sizes of 1,000–4,000 Å, there will be significant limitations in relative ratio, retention, and capacity. In contrast, chromatographic analysis of larger proteins (e.g., 970 kDa) on materials with pore sizes of 60 Å will be unsuccessful because the protein will be excluded from the pore structure of the separation material. Therefore, there exists an optimal range of pore structures for each type of biomolecule.

[0428] Another method for determining the optimal material pore size for a given molecule is to determine the exclusion limit. For example, the exclusion limit in an aqueous SEC is 80 kDa for a 125 Å pore size material, 450 kDa for a 200 Å pore size material, and 1,500 kDa for a 200 Å pore size material (www.waters.com, Waters document 72000338EN, Rev. E, 2015).

[0429] Table 6 To gain a better understanding of the pore sizes required for porous materials used in the chromatographic analysis of biomolecules of different molecular weights and sizes, various models can be used. A model based on reported protein sizes (D. Venturoli, ...) is employed. Am. J. Physiol. Renal Physiol ., 2005, 288 To fit the data in Table 6, use F605, such as Figure 24 As shown. Based on the globular protein model proposed by Rippe ( Kidney Int. 1989,35 Protein size model 2 (1234) best fits these results. Alternatives to hard sphere model 1, spherical model 3, and polydisperse-dextran model 4 of equivalent size do not provide sufficient agreement with the reported biomolecular values. However, model 4 is a good model for approximating the sizes of other polymers.

[0430] use Figure 24 Model 2 in the model can estimate the size of proteins with different molecular weights. For example, 5 kDa proteins are estimated to be 13 Å, and 6 kDa-50 kDa proteins are estimated to be between 14 Å and 32 Å. Comparing the pore size (6 Å-120 Å) of porous materials used for chromatographic analysis of 5 kDa molecules with the molecular size estimated using Model 2, the recommended material pore size is 5-9 times larger than the analyte size. Comparing the expected pore size (200 Å-300 Å) of porous materials used for chromatographic analysis of 50 kDa molecules with the molecular size estimated using Model 2, the recommended material pore size is 6-10 times larger. In the above exclusion limit method, the material pore size is 3-4 times larger than the analyte size estimated using Model 2. Another reference reports on ultrafiltration sieving (EM Renkin, ...). J.Gen.Physio. , 1954, 38 (225), the material pore size is increased by 7-20 times relative to the analyte size (www.sge.com, SGE document TA-0136-H). Next, we define the desired material pore size (DMPD) as a pore size range of 4-9 times the analyte size, representing a lower level of the potential exclusion limit estimated for a given biomolecule (>10 kDa). The DMPD for a given analyte is calculated as a 4-9 times increase relative to the estimated analyte size, rounded to the nearest ten angstroms, as listed in Table 6.

[0431] Similarly, the sizes of other biomolecules, such as Fab (55 kDa, 33 Å, 130-300 Å), Fab2 (bispecific, 110 kDa, 43 Å, 170-390 Å), Fab3 (trispecific, 165 kDa, 50 Å, 200-450 Å), microantibodies (bivalent, 75 kDa, 37 Å, 150-340 Å), tetravalent (tetravalent, 100 kDa, 41 Å, 170-370 Å), trivalent (trivalent, 75 kDa, 37 Å, 150-340 Å), divalent (bispecific, 50 kDa, 31 Å, 130-290 Å), IgG1 (146 kDa, 48 Å, 170-440 Å), and IgG2 (146 kDa, 48 Å, ...), can be estimated with different approximate molecular weights. IgG3 (170 kDa, 50 Å, 200-460 Å), IgG4 (146 kDa, 48 Å, 200-440 Å), IgM (970 kDa, 99 Å, 400-900 Å), IgA1 (160 kDa, 49 Å, 200-450 Å), IgA2 (160 kDa, 49 Å, 200-450 Å), sIgA (385 kDa, 69 Å, 280-621 Å), IgD (184 kDa, 52 Å, 210-470 Å), and IgE (188 kDa, 52 Å, 210-470 Å) were estimated to have different approximate sizes and DMPDs, as indicated in parentheses (approximate molecular weight, estimated molecular size, desired material pore size range).

[0432] By selecting appropriate nanoparticle sizes for the chromatographic separation of specific biomolecules, the method of selecting DMPD was used to modify Examples 1-7.

[0433] Example 10 The methods of Examples 3-9 were modified to be used for DMPD of more than one molecule or biomolecule by using more than one type of silica nanoparticles in the formation of porous layers, as in Scheme 5. Figure 28 As shown.

[0434] Example 11 The methods in Examples 3 and 7-10 are modified to be used for DMPD of more than one molecule or biomolecule by using more than one type of silica nanoparticles in the formation of porous layers, as in Scheme 6. Figure 28 As shown. This method utilizes a hydrothermal treatment step to modify pore properties.

[0435] Example 12 The method of Examples 3-11 was modified to be used for DMPD of more than one molecule or biomolecule by using more than one type of silica nanoparticles in the formation of porous layers. In this method, bi-porous zone materials (surface porous or fully porous) are prepared with or without a hydrothermal treatment step, such as Figure 25 As shown. The inner porous region is prepared as a thicker porous layer with a smaller pore size and a higher surface area. The outer porous region is prepared as a thinner porous layer with a higher pore size. The pore size is selected using the method detailed in Example 8 to greatly exclude larger analytes from the inner porous region. This results in a thinner, high-pore-size porous layer—similar to high-Rho materials used for larger proteins. The inner porous region is designed with a thicker layer, allowing for higher retention and capacity for smaller molecules. Therefore, this biporous material can be considered to have a bicolumn ratio. The column ratio for smaller molecules that can diffuse through both porosity regions is based on the generated SSA and SPV. For the SSA and SPV of the outer porous region, it is necessary to estimate the column ratio for larger molecules excluded from the inner porous region. Such estimation can be performed using the methods detailed in Examples 1-7.

[0436] Example 13 The method of Example 12 was modified to produce bi-porosity zone materials with or without a hydrothermal treatment step, as detailed in Table 7. The methods are applicable to fully porous (e.g., Rho=0) and surface porous materials (e.g., Rho between 0.1 and 0.99). Differences are shown along... Figure 22 The porous layer distance (0→1) is shown. In the table, I = inner region; O = outer region.

[0437] Table 7 Example 14 The methods of Examples 11-13 were modified to produce tri-porosity region materials. Each method is applicable to fully porous (e.g., Rho=0) and surface-porous materials (e.g., Rho between 0.1 and 0.99). Differences in pore size and region thickness along the porous layer distance (0→1) are possible. Materials prepared by this method exhibit an improved range of included analytes and reduce abrupt changes in the chromatographic separation of complex mixtures (e.g., peptides, proteins, RNA, DNA) for analytes partially or completely excluded from specific pore size regions.

[0438] Example 15 The methods in Examples 1-14 are modified to include hydrothermal treatment using the methods of Examples 44-45 of Wyndham {WO 2010 / 141426}, Wyndham (US20130112605, US 20130206665), or optional modifications such as pore reconstruction and pseudomorphic transformation may be implemented (Wyndham, US 8,658,277).

[0439] Example 16 The methods of Examples 1-15 were modified by replacing the non-porous silica core material with an optional core material composition. The optional core material may be a solid or granular material.

[0440] When the optional core is a solid material, it can be changed by Walter (US 7,250,214; US 8,404,346), Wyndham (US 2012055860), Jiang (US 8,791,220), Wyndham (US 8,697,765), Wyndham (US 8,658,2,77), Jung (US 8,680,311), Nakanishi (US 5,624,875), Nakanishi (US 6,207,098), or Guiochon (J). Chromatogr. A , 2007, 1168 The preparation is carried out according to the method detailed in 101). The hybrid bulk material may have pore geometry features that are or are not chromatographically enhancing; it may have ordered or disordered pore structures; it may have ordered or disordered macropores; it may have crystalline or amorphous molecular order; it may have various non-porous, microporous, mesoporous or macroporous structures; and it may have different aspect ratios. The bulk material may be prepared outside the chromatographic apparatus or within the chromatographic apparatus (e.g., a capillary).

[0441] When the optional core material is particulate, it can be spherical or non-spherical. Spherical core materials are formed according to modifications of the method reported in Example 1, or by the core materials described in Examples 1-20 of Barder (US 4,983,369), Unger (US 4,911,903, US 4,775,520), Anderson (US 5,425,930), Wyndham (US 20130112605, US 20130206665), and Lauber (DE 102014019372) as well as the core material described in Example 18. These core materials include, but are not limited to, hybrids of non-porous particles and inorganic compositions (e.g., Choi, JY; Kim, CH; Kim, D. K). J. Am. Ceram. Soc., 1998, 81, 1184-1188. Seog, I. S; Kim, CH J. Mat. Sci. , 1993, 28, 3277-3282), porous materials with pore filling, heat-treated porous materials, rod-shaped materials (e.g., Kievsky), IEEE Transactions on Nanotechnology , 2005, 4, 5, 490), and magnetic materials (e.g., Zhang, Functional Materials Letters , 2010, 3 , 2, 125).

[0442] Non-spherical particles include (but are not limited to) rod-shaped, ring-shaped, granular, helical, capsule-shaped, ring-shaped, disc-shaped, concave disc-shaped, scroll-shaped, ring-shaped, spiral, saddle-shaped, cross-shaped, cubic, dome-shaped derby, spiral, cylindrical, and tubular. Examples of dumbbell-shaped, ring-shaped, rod-shaped, spiral, and spiral icosahedral materials have been reported {Doshi5 N.} PNAS , 2009, 106 ,51, 21495; Alexander, L. Chem. Commun. , 2008, 3507; Naik, S. J. Phys. Chem. C 2007, 111 , 11168;Pang, X. Microporous and Mesoporous Materials 2005, 85 , 1;Kievsky, Y. IEEE Transactions on Nanotechnology , 2005, 4, 5, 490; Sugimoto, T. in Monodispersed Particles, (Elsevier Science BV, Amsterdam) 2001; Ozin, G. Adv. Mater. , 1997,9, 662}.

[0443] The particle size of the core material is 0.1µm-10µm, or 0.5µm-4µm, or 1µm-3.5µm.

[0444] These alternative core materials are composed of one or more of the following: silicon dioxide (0%-100%), hybrid materials (0%-100%), polymers, polymerizable monomers, polyorganosiloxanes, nanoparticles (5nm-200nm), ferromagnetic materials, diamond, aluminum, gold, silver, iron, copper, titanium, niobium, zirconium, cobalt, carbon, graphene, graphite, silicon, silicon carbide, cerium, or any oxide thereof. The use of diamond and gold allows for improved thermal conductivity in these materials. Ferromagnetic and ferrimagnetic materials used include (but are not limited to): magnetite (magnetic iron oxide); hematite; yttrium iron garnet, cobalt, CrO2; and ferrites containing iron and Al, Mg, Ni, Zn, Mn, or Co. These magnetic materials allow for magnetic trapping and handling of these materials. Examples of polyorganosilanes include (but are not limited to) those included in Example 4 and those included in Jiang (US 6,686,035; 7,223,473; 7,919,177) and Wyndham (US 20120141789). Examples of polymers include latex, epoxides, methacrylates, styrene, divinylbenzene, polysaccharides, tree grafts, highly branched polymers, and other substances included in the Polymer Handbook (4th edition, J. Brandrup; EH Immergut; EA Grulke; editor: Wiley: Hoboken, NJ, 1999). Examples of ferrimagnetic and ferromagnetic iron oxide rings and capsules have been reported (Wu, W). J. Phys.Chem. C 2010, 114 , 16092;Jia5 C.-JJ Am. Chem. Soc. 2008, 130 , 16968).

[0445] The optional core material may be further modified before employing one or more of the following: heat treatment in air at 400°C–1,200°C for 10–40 hours to further reduce SPV, or heat treatment in an inert or reducing atmosphere at 400°C–1,200°C for 10–40 hours.

[0446] Alternatively, the core material may be in accordance with US 4,983,369, US 4,911,903, and Giesche ( J. Eur. Ceram. Soc. , 1994, 14,189; J. Eur. Ceram. Soc. , 1994, 14, 205) or Nozawa ( Phys. Rev. E: Slat., Nonlinear, Soft Matter Phys. , 2005, 72The general method described in (1), 011404) is further modified by silica modification. Alternatively, the core material may be modified according to the general method described in Examples 13-15 of Wyndham (US 20130112605, US20130206665).

[0447] Any agglomerated material can be removed by grinding or classification, and the product prepared by this method has little to no porosity. The product prepared by this method is free-flowing and has little to no porosity.

[0448] Example 17 The nanoparticles used in Examples 1-16 were modified to replace some or all of the nanoparticles (5nm-200nm) used with nanoparticles, sols, or nanotubes (5nm-200nm) of hybrids, diamond, aluminum, gold, silver, iron, copper, titanium, niobium, zirconium, cobalt, carbon, graphite, graphene, silicon, silicon carbide, cerium, or any oxide thereof, as detailed in Wyndham (US 20130112605, US 20130206665). The use of diamond nanoparticles allows for improved thermal conductivity in these materials. The ferromagnetic and ferrimagnetic nanoparticles used include (but are not limited to): magnetite (magnetic iron oxide); hematite; yttrium iron garnet, cobalt, CrO2; and ferrites containing iron and Al, Mg, Ni, Zn, Mn, or Co. These magnetic materials allow for magnetic trapping and handling of these materials. Hybrid nanoparticles are prepared by condensation of hybrid inorganic / organic alkoxysilanes, with or without tetraethoxysilanes or tetramethoxysilanes. Similar nanoparticle sizes (e.g., between 5 nm and 100 nm) can be achieved in this method. Alternatively, hybrid nanoparticles can be formed by surface modification of pre-formed silica nanoparticles.

[0449] Example 18 The nanoparticles used in Examples 1-17 were modified to replace some or all of the nanoparticles used with smaller-sized nanoparticles, nanotubes, or molecular precursors (<5 nm), including (but not limited to) single-walled, double-walled, or multi-walled carbon nanotubes, silicon, diamond, aluminum, gold, silver, iron, copper, titanium, niobium, zirconium, cobalt, carbon, graphite, graphene, silicon, silicon carbide, cerium, or any oxide thereof; fullerenes, buckyballs (e.g., buckyballs); quantum dots; or faceted oligomeric silsesquioxanes (POSS), organically modified microsphere silicates, and microsphere silicates. POSS is a unique class of multifunctional hybrid organic / inorganic cluster molecules with RSiO 1.5Functional repeating units have been used in composites, plastic additives, and coatings. Organically modified microsphere silicates and microsphere silicates are silica-based cluster molecules modified by reaction with organosilanes or stabilized with surrounding alkylamine or tetraalkylammonium groups. POSS, organically modified microsphere silicates, and microsphere silicates are well known in the art, commercially available (e.g., Hybrid Plastics, Hattlesburg, MS), and come in a variety of different chemical and molecular structures, as well as different side groups that can be modified for incorporation into materials or for displaying unique surrounding groups (Wyndham, KD, Ph.D. thesis, University of California, Irvine, 2000, p. 256; www.hybridpiastics.com document “POSS User's Guide: A guide to developing new’products with POSS”, version 2.06).

[0450] Interval methods can be implemented as needed to alter porosity and material properties. For example, composites or layered materials containing both diamond and magnetite are beneficial for improving thermal conductivity and magnetic trapping. Materials containing alumina or titanium dioxide are suitable for the separation of glycopeptides, phosphopeptides, and phospholipids. Materials containing cerium dioxide are suitable for the separation of phospholipids and phosphatidylcholine.

[0451] Example 19 The polymeric electrolytes used in Examples 1-19 were modified to include one or more polymeric electrolytes, including (but not limited to): poly(vinylpyrrolidone), poly(diallyldimethylammonium chloride), poly(diallyldimethylammonium bromide), poly(diallyldimethylammonium halide), polyethyleneimine, poly(allylamine hydrochloride), poly(allylamine hydrobromide), poly(allylamine hydrohalide), or any polymeric electrolyte detailed in Wyndham (US 20130112605, US 20130206665). The molecular weights of these polymeric electrolytes varied between 2,000 Da and 500,000 Da.

[0452] Example 20 The polymeric electrolytes used in Examples 1-19 were modified to include the use of chemically degradable polymers, including (but not limited to) polyethylene glycol, polypropylene glycol, polymethacrylate, polymethyl methacrylate, poly(acrylic acid), and polylactic acid-based polymers containing primary, secondary, or tertiary amino side groups, as detailed in Wyndham (US 20130112605, US 20130206665). For example, polyethylene glycol (PEG)-based polyetheramines are described in US 7,101,52, and others are commercially available as Jeffamine polyetheramines (Huntsman Corporation).

[0453] Different methods are employed that do not require heat treatment at 500°C or above. The polymethyl methacrylate network can be decomposed using β-ray radiation. The polymer backbone {Ogino, K} of acrylates and methacrylates with thermally degradable tertiary ester bonds can be decomposed between 180°C and 200°C. Chem. Mater , 1998, 10 , 3833}. It can be degraded by oxidation {Andreozzi, R. Water Research, 1996, 30, 12, 2955; Suzuki, JJ Applied Polymer Science, 1976, 20, 1, 93} and removed by microwave-assisted template using nitric acid and hydrogen peroxide {Tian, ​​B. Chem. Commun. The polyethylene glycol groups are removed by process , 2002, 1186}. A list of other degradable polymer backbones and degradation mechanisms are reported in Degradable Polymers: Principles and Applications {edited by G. Scott and D. Gilead, D., Chapman & Hall (Kluwer) 1995}. Alternatively, surfactants and / or polymers are removed by ozone decomposition or thermal treatment via the process described in Examples 40-43 of Wyndham (US 20130112605, US20130206665).

[0454] Further processing steps can be performed to further reduce and remove polymer content. Any agglomerated or fine materials can be removed by grading.

[0455] Example 21 The methods of Examples 1-20 were modified by replacing the non-porous core material with an optional core material in the form of annular or ring-shaped particles. The composition of this optional core material is the same as that listed in Example 16.

[0456] Figure 26This displays the cross-sectional geometry of porous annular or ring-shaped particles. The key parameter for porous annular particles is defined as the length across the material ring. d 1 -diameter( 2 • l 1 ); d 2 = The diameter of the non-porous core ring spanning the material; d 3 = The diameter spanning the inner empty loop; d 4 = Cross-sectional particle size ( d 4 = d 3 + 2• d 1 = d 3 + 4• l 1 ); c 1 =The center of the material ring (see ½) d 1 (place); l =Spanning the center of the material ring ( c 1 The radius of the material ring surface (1) is also called the short ring radius; 0 = the beginning of the pore along this radius; 1 = the end of the porous layer along this radius. The long ring radius is defined as ½ d 3 + d 1 The aspect ratio of a toroidal ring is defined as the radius of the longer ring divided by the radius of the shorter ring. The aspect ratio of toroidal materials is typically 2-3. For a toroid, the calculated Rho is... d 2 / d 1 In the absence of a porous layer, Rho is 1.

[0457] The particle size of the optional core ring or annular material can be 0.1µm-10µm, or 0.5µm-4µm, or 1µm-3.5µm. The aspect ratio of the optional core ring or annular material can be 2-17, or 2.5-10, or 2.7-5. The diameter of the non-perforated core ring spanning the optional core ring or annular material (…) d 2 The value is 0.1µm-5µm, or 0.5µm-4µm, or 0.7µm-2µm.

[0458] The resulting porous annular or ring-shaped material has a particle size of 0.5µm-44µm, or 0.1µm-10µm, and or 1.3µm-4µm. The aspect ratio of the core annular or ring-shaped material can be 2-13, or 2.1-10, and or 2.2-4. The diameter of the ring spanning the porous material on the annular or ring-shaped surface (…) d 1 The diameter spanning the inner empty ring is 0.1µm-14µm, or 0.5µm-4µm, and possibly 0.8µm-2µm. d 3 The Rho of the porous annular or ring-shaped material is 0.1µm-8.3µm, or 0.3µm-3.5µm, or 0.8µm-2.5µm.

[0459] Annular or circular porous products offer advantages for chromatographic separation. Although not theoretically limited, the primary advantage of this geometry is its permeability due to the presence of internal empty rings (…). d 3 The size increases accordingly. Another advantage of this particle geometry is that it should be related to the diameter of the annular cross-section spanning the porous material of the surface. d 1 (In ring nomenclature, this is equivalent to the short diameter, or twice the short radius) rather than the particle size. d 4 Good correlation with chromatographic efficiency.

[0460] Therefore, compared to other scenarios where commercially available spherical packed materials might be used—where increased column pressure limits particle size to approximately 1.3 µm or larger—higher-efficiency toroidal particles can be produced for use in existing UPLC and UHPLC systems. It is important to note that the column pressure of spherical packed materials is inversely proportional to the square of the particle size and, at optimal linear velocity, inversely proportional to the cube of the particle size. Therefore, using smaller spherical particles allows for improved efficiency (which tends linearly with particle size) and significantly higher column pressure. With toroidal porous particles, it is possible to have a diameter spanning the toroidal cross-section ( d 1 The thickness is 0.5µm-1.0µm, and due to the presence of internal empty loops ( d 3 The column pressure is relatively low.

[0461] It is also possible that the resulting annular surface porous particles are combined with commercially available spherical filler materials (e.g. d 1 Similar efficiency (between 1.6µm and 2.6µm) without the high column pressure associated with spherical filler materials. This is achieved by controlling the diameter of the internal empty rings ( d3 This allows for improved column pressure control. For example, by appropriately selecting a toroidal core material, the resulting surface-porous column can produce higher permeability compared to current possibilities with spherical packed materials that result in lower column pressures. Therefore, UHPLC / UPLC (≤6000 psi system pressure) performance can be achieved with column pressures typically associated with HPLC columns (≤6000 psi system pressure). This allows for a direct scaling-up approach from low-dispersion UHPLC / UPLC systems to more conventional HPLC systems. It is also possible that the resulting toroidal surface-porous particles have similar efficiency to commercially available spherical packed columns, with permeability greater than or equal to that of a monolithic column.

[0462] An additional advantage is the ability to control column pressure for applications where pressure affects retention (e.g., increased retention of peptides or proteins with increasing pressure). It also allows for the possibility of using extremely long columns with exceptionally high column efficiency. Therefore, longer microporous columns, tandem microporous columns, or long capillary columns (10 cm–2,000 cm) can be used to achieve efficiencies greater than 1 million theoretical plates. Such improvements in efficiency offer significant advantages for peptide mapping, proteomics, genomics, lipidomics, petrochemical analysis, and for LC, LC-MS, LC-MS / MS, and SFC.

[0463] Several parameters exist that can be adjusted in the synthesis of surface porous materials based on ring or circular ring core materials. Each can be tuned to improve chromatographic performance, including (but not limited to): efficiency, resolution, column pressure, and pore size required for the application. For example, Table 8 shows constant core material internal porosity (1.5µm) and surface porous shell thickness (0.3µm) for various core ring thicknesses (0.1µm-4.5µm). Table 9 shows constant core material aspect ratio (4) and final Rho (0.70) for various core ring thicknesses (0.1µm-2.5µm). Table 10 shows constant core material aspect ratio (4) and final Rho (0.70) for various core particle sizes (2µm-10µm). d 1 (1.0µm) and Rho (0.70). Table 11 shows constant performance at various core sizes (2µm-10µm). d 1 (1.0µm) and Rho (0.70).

[0464] The mechanical strength of toroidal or circular core materials can be improved by selecting the core material, densifying it at elevated temperatures, and adjusting its aspect ratio. Lower aspect ratio core materials (e.g., between 2 and 3) are expected to be mechanically stronger than those with higher aspect ratios (e.g., between 10 and 15). Less fragile and more adaptable toroidal or circular core materials are sometimes preferred over those that may be more prone to breakage during equipment packing or chromatographic operation.

[0465] The toroidal or circular core material needs to have strong adhesion to the porous layer. When the core material is composed of silica or a hybrid, this can be achieved using the methods detailed in Examples 1-20. When the core material is a polymer, metal, or does not readily form strong adhesion (e.g., covalent bonds) to the porous layer, the core material can be further modified by silica modification, as described in Example 15 or as per US 4,983,369, US 4,911,903, Giesche ( J. Eur Ceram. Soc. ,1994, 14, 189; J. Eur. Ceram. Soc. , 1994, 14, 205) or Nozawa ( Phys. Rev. E: Stat., Nonlinear, Soft Matter Phys. , 2005, 72 (1), 011404) The general method described. Alternatively, the core material may be modified according to the general method described in Examples 13-15 of Wyndham (US 20130112605, US 20130206665).

[0466] Table 8 Table 9 Table 10 Table 11 Example 22 The products of Examples 1-21 may be further processed or modified by one or more of the modification steps in Table 12 below, in any particular order or repeatedly. Representative references are provided for these general operations provided in Table 12. All references are incorporated in full, and exemplary embodiments of selected references are provided.

[0467] Table 12 Example 23 The materials selected from Examples 1-22 have silanol groups that have been surface-modified using reagents of the following types, including (but not limited to) the methods of Wyndham (US 20130112605, US20130206665), Jiang {US 6,686,035; 7,223,473; 7,919,177} and Wyndham {WO 2008 / 103423}: Za (R') b Si-R, in Z = Cl, Br, I, C1-C5 alkoxy, dialkylamino or trifluoromethanesulfonate; a and b are both integers from 0 to 3, provided that a + b = 3; R' is a C1-C6 straight-chain, cyclic, or branched alkyl group, methyl, ethyl, propyl, isopropyl, butyl, tert-butyl, sec-butyl, pentyl, isopentyl, hexyl, and cyclohexyl. R is selected from alkyl, alkenyl, alkynyl, aryl, cyano, amino, glycol, nitro, ester, cation or anion exchange group, pyridyl group, pentafluorophenylalkyl group, alkyl or aryl group containing intercalated polar functional groups, and C1-C 30 Functionalized groups of alkyl groups.

[0468] Advantageous silanol surface-modifying groups include (but are not limited to) octyltrichlorosilane, octadecyltrichlorosilane, octyldimethylchlorosilane, phenylhexyltrichlorosilane, n-butyldimethylchlorosilane, tert-butyldimethylchlorosilane, triisopropylchlorosilane, cyanopropyldiisopropylchlorosilane, pentafluorophenylpropyltrichlorosilane, 2-pyridylethyltrimethoxysilane, and octadecyldimethylchlorosilane.

[0469] Alternatively, the material is surface-modified by forming organic covalent bonds between surface organic groups and a modifying agent. Alternatively, the material is surface-modified by coating with a polymer. Alternatively, the material is surface-modified by a combination of organic group and silanol group modification. Alternatively, the material is surface-modified by a combination of silanol group modification and coating with a polymer. Alternatively, the material is surface-modified by a combination of organic group modification and coating with a polymer. Alternatively, the material is surface-modified by a combination of organic group modification, silanol group modification, and coating with a polymer.

[0470] Example 24 The unbound materials of the selected Examples 1-23 were modified using one or more layers formed from organosiloxanes, mixtures of organosiloxanes and alkoxysilanes, polyorganoalkoxysilanes, hybrid inorganic / organic surrounding materials, or combinations thereof, as described in Example 83 of Wyndham (US 2013011.2605, US 20130206665).

[0471] Example 25 The unbound materials selected in Examples 1-23 were modified by hybridizing the inorganic / organic surrounding materials to generate (SiO2). d / (O 1.5 SiCH2CH2SiO 1.5(where d is 0-30); hybrid inorganic / organic surrounding materials, producing (SiO2). d / (O 1.5 SiCH2CH3), where d is 0-30; or combinations thereof, as described in Example 83 of Wyndham (US 20130112605, US20130206665).

[0472] Example 26 The materials selected from Examples 1, 2, 3, and 7 were subjected to the general methods detailed in Examples 23-24 of Jiang (US 7,223,473), Example 45 of Wyndham (US 20130112605, US 20130206665), or Example 15 of Wyndham (US 2012141789), with surfaces containing C4 (e.g., C4H9) or C8 (e.g., C8H9). 17 The chlorosilane groups were bonded and then end-capped (where applicable) using the general methods of Examples 23-24 of Jiang (US 7,223,473) and Example 16 of Wyndham (US 2012141789). Prototype data are provided in Table 13. Surface coverage was determined by the difference in %C data before and after surface modification.

[0473] Table 13 Example 27 The materials selected from Examples 23 and 26 were packed into chromatographic columns, and the chromatographic performance was evaluated according to the methods of Examples 25-27 of Jiang (US 7,223,473), Examples 17-19 and 33-34 of Wyndham (US 2012141789), and Examples 62-67 of Wyndham (US 20130319086).

[0474] Example 28 According to the TFA, acetonitrile-water gradient method detailed in Examples 62 and 64 of Wyndham (US 20130319086), the peptide 26b packed into a column (2.1 × 50 mm) was chromatographically separated. The peptide mixture was MassPREP peptide standard (Waters Corporation, Milford, MA, P / N 186002337) containing the following: V0 (allantoin), [1] RASG-1, [2] angiotensin fragments 1-7, [3] bradykinin, [4] angiotensin II, [5] angiotensin I, [6] renin substrate, [7] enolase T35, [8] enolase T37, and [9] melitin. The gradient was performed for the mobile phase as follows: (A) 0.05% TFA dissolved in water; (B) 0.05% TEA dissolved in 75:25 acetonitrile / water (v / v). The gradient characteristics were as follows: on an ACQUITY UPLC system (Waters Corporation, Milford, MA) at ambient temperature (0.2 mL / min) and 220 nm, 0.93% to 66.7% B was maintained for 30 min; 66.7% B was maintained for 2 min; and 100% A was maintained for 18 min.

[0475] equivalent Those skilled in the art will recognize or be able to determine various equivalents of the specific embodiments of the invention described herein using no more than conventional experiments. Such equivalents are intended to be covered by this invention.

[0476] By incorporating via reference All publications, patent applications and patents specified herein are expressly incorporated herein by reference in their entirety.

Claims

1. A chromatographic material comprising a chromatographic core material having a main surface and a multilayer chromatographic surface material, wherein each layer of the multilayer chromatographic surface material independently has an average pore size of 20 angstroms to 1500 angstroms, wherein the average pore size of each layer of the multilayer chromatographic surface material varies in a certain pattern as the distance from the main surface of the chromatographic core material to the outermost surface of the chromatographic material increases, wherein the pattern is selected from conical, tapered, conical, flared, and combinations thereof, wherein the pattern is defined by an average pore size map as the distance traveled from the main surface of the chromatographic core material to the outermost surface of the chromatographic material increases.

2. The chromatographic material according to claim 1, wherein the material is in particulate form.

3. The chromatographic material according to claim 1, wherein the material is in bulk form.

4. The chromatographic material according to claim 1, wherein the material is in the form of a surface porous material.

5. The chromatographic material according to claim 1, wherein the chromatographic core material is an inorganic material, an organic material, or an inorganic / organic hybrid material.

6. The chromatographic material according to claim 5, wherein the chromatographic core material has the following formula: Mode: (SiO2) d / [R 2 ((R) p (R 1 ) q SiO t ) m ] (I) in, R and R 1 Each independently is C1-C 18 Alkoxy, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 is C1-C 18 alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl, C3-C 18 cycloalkyl, C1-C 18 heterocycloalkyl, C5-C 18 aryl, C1-C 18 heteroaryl; or is absent; wherein each R 2 is attached to two or more silicon atoms; p and q are each independently between 0.0 and 3.

0. t is 0.5, 1.0, or 1.5; d ranges from 0 to approximately 30; m is an integer from 1 to 20; where R and R are integers. 1 and R 2 To be arbitrarily replaced; The prerequisite is: (1) when R 2 When it does not exist, m=1, and At this time 0 <p+q≤3; as well as (2) When R 2 When it exists, m = 2 to 20, and At this point, p + q ≤ 2; Mode: (SiO2) d / [(R) p (R 1 ) q SiO t ] (II) in, R and R 1 Each independently is C1-C 18 Alkoxy, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; d ranges from 0 to approximately 30; p and q are each independently between 0.0 and 3.0, provided that when p + q = 1, then t = 1.5; when p + q = 2, then t = 1; or when p + q = 3, then t = 0.5; or Mode: (SiO2) d / [R 2 ((R 1 ) r SiO t ) m ] (III) in, R 1 For C1-C 18 Alkoxy, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C1-C 18 Heteroaryl; or not present; wherein each R 2 Connected to two or more silicon atoms; d ranges from 0 to approximately 30; r can be 0, 1, or 2, provided that when r = 0, then t = 1.5; when r = 1, then t = 1; or when r = 2, then t = 0.5; and m is an integer from 1 to 20.

7. The chromatographic material according to claim 1, wherein each of one or more layers of the chromatographic surface material independently has a thickness of 25 μm. 2 / g to 1100m 2 Specific surface area per g.

8. The chromatographic material according to claim 1, wherein each of one or more layers of the chromatographic surface material independently has a thickness of 0.15 cm. 3 / g to 1.5cm 3 / g average pore volume.

9. The chromatographic material according to claim 1, wherein at least one layer of one or more layers of the chromatographic surface material is an inorganic / organic hybrid material comprising hydrophobic surface groups and one or more ionizable modifiers.

10. The chromatographic material according to claim 9, wherein each ionizable modifier independently comprises a carboxylic acid group, a sulfonic acid group, an aryl sulfonic acid group, a phosphate group, a boric acid group, an amino group, an imino group, an amide group, a pyridyl group, an imidazolyl group, a ureyl group, a thionyl-ureyl group, or an aminosilyl group.

11. The chromatographic material of claim 1, wherein the material further comprises surface modification, and wherein the material is surface modified by coating a polymer, by a combination of organic groups and silanol groups.

12. A chromatography apparatus, comprising: a) Internal channels for receiving filler material, and b) A packed chromatographic bed comprising the chromatographic material according to any one of claims 1-11.

13. A chromatographic material having controlled porosity, comprising a chromatographic core material having a main surface and a multilayer chromatographic surface material, wherein each layer of the multilayer chromatographic surface material independently has an average pore size of 20 Å to 1500 Å, wherein the average pore size of the multilayer chromatographic surface material varies from the main surface of the chromatographic core material to the outermost surface of the chromatographic material in a predetermined pattern, wherein the predetermined pattern includes either an increase in average pore size from the main surface of the chromatographic core material to the outermost surface of the chromatographic material, or a decrease in average pore size from the main surface of the chromatographic core material to the outermost surface of the chromatographic material, wherein each layer of the multilayer chromatographic surface material independently has an average pore size of 25 μm. 2 / g to 1100m 2 / g specific surface area, wherein the specific surface area of ​​the multilayer chromatographic surface material varies from the main surface of the chromatographic core material to the outermost surface of the chromatographic material in a predetermined pattern, and wherein controlled porosity is achieved by Ostwald ripening.

14. The chromatographic material according to claim 13, wherein the material is in particulate form.

15. The chromatographic material according to claim 13, wherein the material is in bulk form.

16. The chromatographic material according to claim 13, wherein the material is in the form of a surface porous material.

17. The chromatographic material according to claim 13, wherein the chromatographic core material is an inorganic material, an organic material, or an inorganic / organic hybrid material.

18. The chromatographic material according to claim 17, wherein the chromatographic core material has the following formula: Mode: (SiO2) d / [R 2 ((R) p (R 1 ) q SiO t ) m ] (I) in, R and R 1 Each independently is C1-C 18 Alkoxy, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C1-C 18 Heteroaryl; or not present; wherein each R 2 Connected to two or more silicon atoms; p and q are each independently between 0.0 and 3.

0. t is 0.5, 1.0, or 1.5; d ranges from 0 to approximately 30; m is an integer from 1 to 20; where R and R are integers. 1 and R 2 To be arbitrarily replaced; The prerequisite is: (1) when R 2 When it does not exist, m=1, and At this time 0 <p+q≤3; as well as (2) When R 2 When it exists, m = 2 to 20, and At this point, p + q ≤ 2; Mode: (SiO2) d / [(R) p (R 1 ) q SiO t ] (II) in, R and R 1 Each independently is C1-C 18 Alkoxy, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; d ranges from 0 to approximately 30; p and q are each independently between 0.0 and 3.0, provided that when p + q = 1, then t = 1.5; when p + q = 2, then t = 1; or when p + q = 3, then t = 0.5; or Mode: (SiO2) d / [R 2 ((R 1 ) r SiO t ) m ] (III) in, R 1 For C1-C 18 Alkoxy, C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C5-C 18 aryloxy group, or C1-C 18 Mixed aromatics; R 2 For C1-C 18 Alkyl, C2-C 18 alkenyl, C2-C 18 alkynyl group, C3-C 18 cycloalkyl, C1-C 18 Heterocyclic alkyl, C5-C 18 Aryl, C1-C 18 Heteroaryl; or not present; wherein each R 2 Connected to two or more silicon atoms; d ranges from 0 to approximately 30; r can be 0, 1, or 2, provided that when r = 0, then t = 1.5; when r = 1, then t = 1; or when r = 2, then t = 0.5; and m is an integer from 1 to 20.

19. The chromatographic material of claim 13, wherein the predetermined mode includes an increase in specific surface area from the main surface of the chromatographic core material to the outermost surface of the chromatographic material.

20. The chromatographic material of claim 13, wherein the predetermined mode includes a decrease in specific surface area from the main surface of the chromatographic core material to the outermost surface of the chromatographic material.

21. The chromatographic material according to claim 13, wherein each layer of the multilayer chromatographic surface material independently has a thickness of 0.15 cm. 3 / g to 1.5cm 3 / g average pore volume, and wherein the average pore volume of the multilayer chromatographic surface material varies from the main surface of the chromatographic core material to the outermost surface of the chromatographic material in a predetermined pattern.

22. The chromatographic material of claim 21, wherein the predetermined pattern includes an increase in average pore volume from the main surface of the chromatographic core material to the outermost surface of the chromatographic material.

23. The chromatographic material of claim 21, wherein the predetermined mode includes a decrease in average pore volume from the main surface of the chromatographic core material to the outermost surface of the chromatographic material.

24. The chromatographic material according to claim 13, wherein at least one layer of the multilayer chromatographic surface material is an inorganic / organic hybrid material comprising hydrophobic surface groups and a variety of ionizable modifiers.

25. The chromatographic material according to claim 24, wherein each ionizable modifier independently comprises a carboxylic acid group, a sulfonic acid group, an aryl sulfonic acid group, a phosphate group, a boric acid group, an amino group, an imino group, an amide group, a pyridyl group, an imidazolyl group, a ureyl group, a thionyl-ureyl group, or an aminosilyl group.

26. The chromatographic material of claim 13, wherein the material further comprises surface modification, and wherein the material is surface modified by coating a polymer, by a combination of organic groups and silanol groups.

27. A chromatography apparatus, comprising: a) Internal channels for receiving filler material, and b) A packed chromatographic bed comprising the chromatographic material according to any one of claims 13-26.

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