Stable granular compositions

Abstract

This article provides compositions comprising multiple particles, methods for preparing compositions comprising multiple particles, and related uses, kits, and articles thereof.

Description

Technical Field

[0001] This disclosure relates to compositions comprising particles, and methods, uses, kits and articles thereof. Background Technology

[0002] Particles, such as microbeads, are widely used in research, diagnostics, industry, medicine, and other fields to bind ligands, lyse cells, homogenize tissues, localize or separate molecules (e.g., on arrays), perform bead-on reactions, and many other uses. For example, silica beads are commonly used to bind and separate DNA or RNA.

[0003] The granules are typically supplied in the form of dried or lyophilized compositions, or as aqueous suspensions. However, drying or lyophilizing the granules can lead to granule aggregation or degradation, as well as resuspension issues. Aqueous suspensions of the granules may cause granule sedimentation, which can result in aggregation and clumping, requiring continuous mixing to ensure consistency during use, and may also cause bead stability issues.

[0004] Therefore, there is a need in the art for compositions that support or enhance particle stability, functionality, storage, and handling.

[0005] All references cited in this article, including patent applications and publications, are incorporated herein by reference in their entirety. Summary of the Invention

[0006] In some aspects, this document provides compositions comprising multiple particles. In some embodiments, the composition comprises multiple particles and one, two, or all three of the following: a mobile phase, a viscosity enhancer, and a solubilizer. In some embodiments, the composition comprises multiple particles and a mobile phase. In some embodiments, the composition comprises multiple particles and a viscosity enhancer. In some embodiments, the composition comprises multiple particles and a solubilizer. In some embodiments, the composition comprises multiple particles, a mobile phase, and a viscosity enhancer. In some embodiments, the composition comprises multiple particles, a mobile phase, and a solubilizer. In some embodiments, the composition comprises multiple particles, a viscosity enhancer, and a solubilizer. In some embodiments, the mobile phase comprises a suspending agent.

[0007] In some embodiments, the composition comprises a plurality of particles and (a) a mobile phase containing a suspending agent; (b) a viscosity enhancer; and (c) a solubilizer.

[0008] In some embodiments, the concentration of the mobile phase is between about 60% and about 99% by weight, between about 65% and about 95%, between about 70% and about 90%, between about 75% and about 90%, or between about 80% and about 90% (w / w). In some embodiments, the concentration of the mobile phase is about 70%, about 80%, or about 90% w / w. In some embodiments, the concentration of the mobile phase is about 80% w / w. In some embodiments, the suspending agent is a sugar alcohol, a glycol, a water-miscible polymer, an aprotic solvent, or any combination thereof. In some embodiments, the sugar alcohol is glycerol, sorbitol, erythritol, threitol, arabinitol, xylitol, ribitol, mannitol, galactitol, fucitol, idutol, inositol, volemitol, isomaltitol, maltitol, lactitol, maltotriol, maltotetratitol, polyglycitol, or any combination thereof. In some embodiments, the sugar alcohol is glycerol. In some embodiments, the concentration of glycerol in the composition is about 80% w / w. In some embodiments, the diol is diethylene glycol, ethylene glycol, hexanediol, propylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, glycol ether, or any combination thereof. In some embodiments, the diol is propylene glycol. In some embodiments, the water-miscible polymer is an acrylic polymer, an ether polymer, an epoxy polymer, a polyethylene polymer, a polyethylene glycol polymer, a polystyrene polymer, a polyvinyl chloride polymer, a polytetrafluoroethylene polymer, a polydimethylsiloxane polymer, a polyester polymer, a poly(N-vinylpyrrolidone) polymer, a polystyrene copolymer, a polyurethane polymer, or any combination thereof. In some embodiments, the water-miscible polymer is a polyethylene glycol (PEG) polymer. In some embodiments, the water-miscible polymer has an average molecular weight of about 1000 g / mol or less, about 900 g / mol or less, about 800 g / mol or less, about 700 g / mol or less, about 600 g / mol or less, about 500 g / mol or less, about 400 g / mol or less, about 300 g / mol or less, about 200 g / mol or less, or about 100 g / mol or less. In some embodiments, the water-miscible polymer comprises an average molecular weight between about 100 g / mol and about 1000 g / mol, between about 200 g / mol and about 600 g / mol, between about 200 g / mol and about 400 g / mol, or between about 200 g / mol and about 300 g / mol. In some embodiments, the water-miscible polymer comprises an average molecular weight of about 200 g / mol or about 300 g / mol.In some embodiments, the water-miscible polymer is PEG 200 and / or PEG 300. In some embodiments, the aprotic solvent is a polar aprotic solvent, optionally a dipolar aprotic solvent. In some embodiments, the aprotic solvent is dimethyl sulfoxide (DMSO), dimethyl sulfone, diphenyl sulfone (DPS), diethylene sulfoxide, diethyl sulfone, diisopropyl sulfone, sulfolane, tetrahydrothiophene-1-monooxide, N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), or any combination thereof. In some embodiments, the aprotic solvent is sulfolane.

[0009] In some embodiments, the viscosity enhancer is at least partially soluble in the mobile phase. In some embodiments, the concentration of the viscosity enhancer is between about 1% and about 40%, between about 1% and about 35%, between about 1% and about 30%, between about 1% and about 25%, between about 1% and about 20%, between about 1% and about 15%, between about 1% and about 10%, or between about 1% and about 5% w / w. In some embodiments, the concentration of the viscosity enhancer is about 5% w / w. In some embodiments, the viscosity enhancer comprises a water-miscible polymer. In some embodiments, the water-miscible polymer comprises an average molecular weight of at least about 2000 g / mol, at least about 4000 g / mol, at least about 5000 g / mol, at least about 6000 g / mol, at least about 7000 g / mol, at least about 8000 g / mol, at least about 9000 g / mol, at least about 10000 g / mol, at least about 12000 g / mol, at least about 14000 g / mol, at least about 16000 g / mol, at least about 18000 g / mol, at least about 20000 g / mol, at least about 25000 g / mol, or at least about 30000 g / mol. In some embodiments, the water-miscible polymer comprises an average molecular weight between about 2000 g / mol and about 30000 g / mol, between about 4000 g / mol and about 20000 g / mol, between about 4000 g / mol and about 10000 g / mol, or between about 4000 g / mol and about 8000 g / mol. In some embodiments, the water-miscible polymer comprises an average molecular weight of about 4000 g / mol, about 8000 g / mol, about 10000 g / mol, or about 20000 g / mol. In some embodiments, the water-miscible polymer is an acrylic polymer, an ether polymer, an epoxy polymer, a polyethylene polymer, a polyethylene glycol polymer, a polystyrene polymer, a polyvinyl chloride polymer, a polytetrafluoroethylene polymer, a polydimethylsiloxane polymer, a polyester polymer, a poly(N-vinylpyrrolidone) polymer, a polystyrene copolymer, a polyurethane polymer, or any combination thereof. In some embodiments, the water-miscible polymer comprises a polyethylene glycol (PEG) polymer. In some embodiments, the PEG polymer is PEG 4000, PEG 8000, PEG 10000, PEG 20000, or any combination thereof. In some embodiments, the PEG polymer is PEG 8000. In some embodiments, the concentration of PEG 8000 in the composition is about 5% w / w. In some embodiments, the viscosity enhancer comprises polyvinyl alcohol (PVA).In some embodiments, the viscosity enhancer comprises sulfone or a sulfone polymer.

[0010] In some embodiments, the solubilizer is at least partially soluble in the mobile phase. In some embodiments, the solubilizer is water-soluble. In some embodiments, the concentration of the solubilizer is between about 1% and about 40%, between about 5% and about 30%, between about 10% and about 25%, or between about 10% and about 20% w / w. In some embodiments, the concentration of the solubilizer is about 15% w / w. In some embodiments, the solubilizer comprises a dissociating agent. In some embodiments, the dissociating agent is n-butanol, ethanol, guanidine salts, lithium perchlorate, lithium acetate, magnesium chloride, phenol, 2-propanol, sodium dodecyl sulfate, thiourea, urea, water-soluble urea derivatives, or any combination thereof. In some embodiments, the dissociating agent is a guanidine salt. In some embodiments, the guanidine salt is guanidine chloride, guanidine sulfate, guanidine carbonate, guanidine nitrate, guanidine isothiocyanate, guanidine thiocyanate, or any combination thereof. In some embodiments, the dissociating agent is urea and / or water-soluble urea derivatives. In some embodiments, the concentration of the urea and / or water-soluble urea derivative in the composition is about 15% w / w. In some embodiments, the water-soluble urea derivative is thiourea, hydroxyurea, dimethylurea, or any combination thereof. In some embodiments, the solubilizer comprises a buffer. In some embodiments, the buffer is MES, Bis-Tris, ADA, ACES, PIPES, MOPSO, Bis-Tris propane, BES, MOPS, TES, HEPES, DIPSO, MOBS, TAPSO, Tris, HEPPSO, POPSO, TEA, EPPS, HEPPS, Tricine, Gly-Gly, Bicine, HEPBS, TAPS, AMPD, TABS, AMPSO, CHES, CAPSO, AMP, CAPS, CABS, phosphate, maleate, glycine, citrate, formate, succinate, acetate, propionate, pyridine, piperazine, carcoate, histidine, ethanolamine, carbonate, imidazole, pyrophosphate, hydrazine, taurine (AES), borate, ammonium hydroxide, methylamine, piperidine, malate buffer, or any combination thereof. In some embodiments, the buffer comprises TAPS, HEPES, or MOPS buffer, or any combination thereof.

[0011] In some embodiments, the suspending agent comprises glycerol, the viscosity enhancer comprises PEG 8000, and the solubilizer comprises urea. In some embodiments, the concentration of glycerol is about 80% w / w, the concentration of PEG 8000 is about 5% w / w, and the concentration of urea is about 15% w / w. In some embodiments, the ratio of glycerol:PEG 8000:urea in the composition is 16:1:3 w / w. In some embodiments, the pH of the composition is between about 7 and about 8.

[0012] In some embodiments, the composition has the following viscosity: when measured at a temperature of about 15°C, between about 7000 mPa·s and about 8000 mPa·s, between about 7250 mPa·s and about 8000 mPa·s, between about 7500 mPa·s and about 8000 mPa·s, or between about 7750 mPa·s and about 8000 mPa·s; when measured at a temperature of about 20°C, between about 5000 mPa·s and about 6000 mPa·s, between about 5250 mPa·s and about 6000 mPa·s, between about 5500 mPa·s and about 6000 mPa·s, or between about 5500 mPa·s and about 5750 mPa·s; when measured at a temperature of about 25°C, between about 5500 mPa·s and about 7000 mPa·s. Between approximately 5750 mPa·s and approximately 6750 mPa·s, or between approximately 6000 mPa·s and approximately 6500 mPa·s; when measured at a temperature of approximately 30°C, between approximately 4250 mPa·s and approximately 5500 mPa·s, between approximately 4500 mPa·s and approximately 5500 mPa·s, between approximately 4750 mPa·s and approximately 5250 mPa·s, or between approximately 4750 mPa·s and approximately 5000 mPa·s; when measured at a temperature of approximately 35°C, between approximately 2000 mPa·s and approximately 3000 mPa·s, between approximately 2250 mPa·s and approximately 2750 mPa·s, or between approximately 2250 mPa·s and approximately 2500 mPa·s; when measured at a temperature of approximately 40°C, between approximately 750 mPa·s and approximately 1750 mPa·s. Between approximately 1000 mPa·s and approximately 1750 mPa·s, or between approximately 1000 mPa·s and approximately 1500 mPa·s; when measured at a temperature of approximately 45°C, between approximately 500 mPa·s and approximately 1500 mPa·s, between approximately 750 mPa·s and approximately 1250 mPa·s, or between approximately 1000 mPa·s and approximately 1250 mPa·s; when measured at a temperature of approximately 50°C, between approximately 250 mPa·s and approximately 1500 mPa·s, between approximately 500 mPa·s and approximately 1250 mPa·s, or between approximately 500 mPa·s and approximately 1000 mPa·s; when measured at a temperature of approximately 55°C, between approximately 500 mPa·s and approximately 1500 mPa·s, between approximately 750 mPa·s and approximately 1250 mPa·s. Between mPa·s, or between about 1000 mPa·s and about 1250 mPa·s;And / or when measured at a temperature of about 60°C, the viscosity is between about 100 mPa·s and about 600 mPa·s, between about 200 mPa·s and about 500 mPa·s, or between about 200 mPa·s and about 400 mPa·s. In some embodiments, a rotational viscometer is used to evaluate the viscosity of the composition. In some embodiments, the viscosity of the composition is evaluated at a shaft rotation speed of about 10 revolutions per minute (RPM).

[0013] In some embodiments, the density of the composition is between about 0.5 g / mL and about 2 g / mL, between about 1 g / mL and about 2 g / mL, between about 1 g / mL and about 1.5 g / mL, or between about 1.1 g / mL and about 1.5 g / mL. In some embodiments, the density of the composition is about 1.3 g / mL. In some embodiments, the density of the composition is assessed on an analytical balance.

[0014] In some embodiments, the mobile phase is non-aqueous or substantially non-aqueous. In some embodiments, the composition is non-aqueous or substantially non-aqueous. In some embodiments, the water content of the composition is about 1% or less. In some embodiments, the water content is assessed by Karl Fischer titration.

[0015] In some embodiments, the composition is a liquid composition.

[0016] In some embodiments, the plurality of particles comprises one or more particles configured to bind nucleic acids, peptides, lipids, carbohydrates, or small molecules. In some embodiments, the plurality of particles comprises one or more particles configured to bind DNA and / or RNA. In some embodiments, the plurality of particles comprises one or more microparticles, nanoparticles, microspheres, paramagnetic beads, magnetic beads, microbeads, nanobeads, or any combination thereof. In some embodiments, the plurality of particles comprises one or more silica beads, silica gel beads, controlled-porosity glass beads, magnetic beads, glass beads, paramagnetic beads, Dynabeads immunomagnetic beads, Sephadex / Sepharose beads, cellulose beads, polystyrene beads, mineral beads, crystalline particles, zircon particles, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof. In some embodiments, one or more of the plurality of particles are functionalized. In some embodiments, one or more particles are surface-functionalized with carboxyl, amino, hydroxyl, silica, streptavidin, endopeptidase moiety, amine, thiol, glycol, polymer, antibody or antibody fragment, nucleic acid, oligonucleotide, peptide, polypeptide, or any combination thereof. In some embodiments, the plurality of particles comprise magnetic silica beads. In some embodiments, the plurality of particles are present in the composition at a concentration of at least about 0.5%, at least about 1%, at least about 2.5%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 30% by weight / volume (w / v). In some embodiments, the plurality of particles are present in the composition at a concentration between about 0.5% and about 30% w / v, between about 1% and about 25% w / v, between about 2.5% and about 20% w / v, or between about 5% and about 15% w / v. In some embodiments, the plurality of particles are present in the composition at a concentration of about 10% w / v.

[0017] In some embodiments, the composition enhances the stability of particles in a plurality of particles. In some embodiments, the composition enhances the stability of particles in a plurality of particles compared to corresponding particles in an aqueous solution. In some embodiments, the plurality of particles in the composition are stable for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months. In some embodiments, particle stability is assessed based on particle integrity, particle aggregation, and / or retention of ligand binding capacity. In some implementations, compared to a baseline, the particles among the plurality of particles maintain at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 95%, at least about 95%, or at least about 99% ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% of the ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 8 months, at least about 9 months, at least about 95%, or at least about 99% of the ligand binding capacity. In some embodiments, the composition enhances ligand binding of the particles in the plurality of particles by at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% compared to corresponding particles in an aqueous solution. In some embodiments, the plurality of particles comprises particles capable of binding nucleic acid ligands. In some embodiments, the stability of the particles is assessed based on nucleic acid ligand binding capacity compared to a baseline and / or to corresponding particles in an aqueous solution. In some embodiments, the nucleic acid ligand comprises DNA and / or RNA. In some embodiments, the plurality of particles comprises silica particles. In some embodiments, the plurality of particles comprises magnetic silica particles.In some implementations, compared to a baseline, the particles among the plurality of particles maintain at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 95%, or at least about 99% of their nucleic acid ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% of their nucleic acid ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months. In some embodiments, the composition enhances the binding of nucleic acid ligands to particles in a plurality of particles by at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% compared to corresponding particles in an aqueous solution. In some embodiments, particle stability is evaluated at room temperature. In some embodiments, particle stability is evaluated at a temperature between about 20°C and about 30°C. In some embodiments, particle stability is evaluated at a temperature of about 25°C. In some embodiments, particle stability is evaluated under normal atmospheric conditions, under low oxygen conditions, or in nitrogen. In some embodiments, the composition is capable of adhering to a polypropylene surface. In some embodiments, the composition has microbiological stability for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months.

[0018] In some embodiments, the composition further comprises agents such as antioxidants, reducing agents, chelating agents, or any combination thereof. In some embodiments, the composition does not contain antimicrobial agents. In some embodiments, the composition contains less than about 10% surfactant or detergent. In some embodiments, the composition does not contain surfactant or detergent.

[0019] On the other hand, this document provides a method for preparing a composition comprising a plurality of particles, comprising: (a) providing a plurality of particles; and (b) suspending the plurality of particles in a formulation comprising one, two, or all three of the following: a mobile phase (e.g., a mobile phase comprising a suspending agent), a viscosity enhancer, and a solubilizer.

[0020] On the other hand, this document provides a method for preparing a composition comprising a plurality of particles, comprising: (a) providing a plurality of particles; and (b) suspending said plurality of particles in a formulation comprising: (i) a mobile phase comprising a suspending agent; (ii) a viscosity enhancer; and (iii) a solubilizer.

[0021] In some embodiments, the plurality of particles provided in step (a) are dehydrated or freeze-dried. In some embodiments, the method further includes dehydrating or freeze-drying the plurality of particles prior to step (a).

[0022] In some embodiments, the dehydration includes suspending a plurality of particles in a first organic solvent. In some embodiments, the dehydration includes: (i) separating a plurality of particles stored in an aqueous solution from the aqueous solution, and (ii) suspending the separated plurality of particles in a first volume of a first organic solvent. In some embodiments, the dehydration further includes: (1) separating a plurality of particles from the first organic solvent, and (2) resuspending the separated plurality of particles in another volume of the first organic solvent. In some embodiments, the method includes repeating steps (1) and (2) at least once, at least twice, or more times.

[0023] In some embodiments, the dehydration includes: (i) separating a plurality of particles stored in an aqueous solution from the aqueous solution, and (ii) suspending the separated plurality of particles in a series of volumes of a first organic solvent, wherein the volumes in the series contain an increasing amount of the first organic solvent, wherein the first volume in the series contains an organic solvent concentration between about 20% and about 80%, and the last volume in the series contains about 100% of the organic solvent concentration. In some embodiments, the first volume in the series contains about 50% of the organic solvent concentration, and the last volume in the series contains about 100% of the organic alcohol concentration. In some embodiments, the series of volumes contains about 2 to about 15 volumes, about 2 to about 10 volumes, or about 5 to about 7 volumes. In some embodiments, the first organic solvent contains an alcohol, optionally wherein the alcohol is ethanol and / or isopropanol.

[0024] In some embodiments, the first organic solvent comprises an organic solvent miscible with water and / or highly soluble in water. In some embodiments, the first organic solvent comprises: a polar aprotic solvent, optionally wherein said polar aprotic solvent is DMSO, tetrahydrofuran (THF), acetonitrile, propylene carbonate, sulfolane, and any combination thereof; a water-miscible p- or E-type glycol ether, optionally wherein said first organic solvent comprises dipropylene glycol methyl ether and / or diethylene glycol ethyl ether; an alcohol, optionally wherein said alcohol is ethanol and / or isopropanol; tetrahydrothiophene 1-oxide; or any combination thereof. In some embodiments, the first organic solvent comprises a mixture of two or more solvents, optionally wherein said solvents are in a ratio of about 1:1, and further optionally wherein said mixture comprises: DMSO and ethanol; DMSO and isopropanol; or DMSO and THF. In some embodiments, the first organic solvent comprises DMSO. In some embodiments, the first organic solvent comprises an alcohol, optionally wherein said alcohol is ethanol and / or isopropanol.

[0025] In some embodiments, step (b) includes: (i) separating a plurality of particles from a first organic solvent of a given volume, and (ii) suspending the separated plurality of particles in a given volume of the formulation.

[0026] In some embodiments, the method further includes, prior to step (b), suspending a plurality of particles in a first volume of solution comprising a second organic solvent and a suspending agent. In some embodiments, the method further includes, prior to step (b): (i) separating the plurality of particles from a volume of the first organic solvent, and (ii) suspending the separated plurality of particles in a first volume of solution comprising a second organic solvent and a suspending agent. In some embodiments, the method further includes: (1) separating the plurality of particles from the solution, and (2) resuspending the separated plurality of particles in another volume of the solution. In some embodiments, the method includes repeating steps (1) and (2) at least once, at least twice, or more times.

[0027] In some embodiments, the second organic solvent and the suspending agent in the solution are in a ratio of about 1:1.

[0028] In some embodiments, the suspending agent is a sugar alcohol, a glycol, a water-miscible polymer, an aprotic solvent, or any combination thereof. In some embodiments, the sugar alcohol is glycerol, sorbitol, erythritol, threitol, arabinitol, xylitol, ribitol, mannitol, galactitol, fucitol, idoteol, inositol, heptaheptaol, isomaltitol, maltitol, lactitol, maltotriol, maltotetratitol, polyglycol, or any combination thereof, optionally wherein the sugar alcohol is glycerol; the diol is diethylene glycol, ethylene glycol, hexanediol, propylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, glycol ether, or any combination thereof; optionally wherein the diol is propylene glycol; the water-miscible polymer is an acrylic polymer, ether polymer, epoxy polymer, polyethylene glycol polymer, polystyrene polymer, polyvinyl chloride polymer, polytetrafluoroethylene polymer, polydimethylsiloxane polymer, polyester polymer, poly(N-vinylpyrrolidone) polymer, polystyrene copolymer, polyurethane polymer, or any combination thereof, optionally wherein the water-miscible polymer is PEG. 200 and / or PEG 300; and / or the aprotic solvent is a polar aprotic solvent, optionally wherein the aprotic solvent is sulfolane. In some embodiments, the suspending agent comprises glycerol.

[0029] In some embodiments, the second organic solvent comprises an organic solvent miscible with water and / or highly soluble in water. In some embodiments, the second organic solvent comprises: a polar aprotic solvent, optionally said polar aprotic solvent is DMSO, tetrahydrofuran (THF), acetonitrile, propylene carbonate, sulfolane, and any combination thereof; a water-miscible p- or E-type glycol ether, optionally said second organic solvent comprises dipropylene glycol methyl ether and / or diethylene glycol ethyl ether; an alcohol, optionally said alcohol is ethanol and / or isopropanol; or tetrahydrothiophene 1-oxide. In some embodiments, the second organic solvent comprises a mixture of two or more solvents, optionally said solvents in a ratio of about 1:1, and further optionally said mixture comprises: DMSO and ethanol; DMSO and isopropanol; or DMSO and THF. In some embodiments, the second organic solvent comprises DMSO.

[0030] In some embodiments, the second organic solvent is the same as the first organic solvent; or the second organic solvent is different from the first organic solvent. In some embodiments, the first and second organic solvents comprise DMSO.

[0031] In some embodiments, step (b) includes: (i) separating a plurality of particles from a volume of the solution containing a second organic solvent and a suspending agent, and (ii) suspending the separated plurality of particles in a volume of the formulation.

[0032] In some embodiments, the concentration of the mobile phase is between about 60% and about 99% by weight, between about 65% and about 95%, between about 70% and about 90%, between about 75% and about 90%, or between about 80% and about 90% (w / w). In some embodiments, the concentration of the mobile phase is about 70%, about 80%, or about 90% w / w. In some embodiments, the concentration of the mobile phase is about 80% w / w. In some embodiments, the suspending agent is a sugar alcohol, a glycol, a water-miscible polymer, an aprotic solvent, or any combination thereof. In some embodiments, the sugar alcohol is glycerol, sorbitol, erythritol, threitol, arabinitol, xylitol, ribitol, mannitol, galactitol, fucitol, idotitol, inositol, heptaheptaol, isomaltitol, maltitol, lactitol, maltotriol, maltotetratitol, polyglycol, or any combination thereof. In some embodiments, the sugar alcohol is glycerol. In some embodiments, the concentration of glycerol in the composition is about 80% w / w. In some embodiments, the diol is diethylene glycol, ethylene glycol, hexanediol, propylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, glycol ethers, or any combination thereof. In some embodiments, the diol is propylene glycol. In some embodiments, the water-miscible polymer is an acrylic polymer, an ether polymer, an epoxy polymer, a polyethylene polymer, a polyethylene glycol polymer, a polystyrene polymer, a polyvinyl chloride polymer, a polytetrafluoroethylene polymer, a polydimethylsiloxane polymer, a polyester polymer, a poly(N-vinylpyrrolidone) polymer, a polystyrene copolymer, a polyurethane polymer, or any combination thereof. In some embodiments, the water-miscible polymer is a polyethylene glycol (PEG) polymer. In some embodiments, the water-miscible polymer comprises an average molecular weight of about 1000 g / mol or less, about 900 g / mol or less, about 800 g / mol or less, about 700 g / mol or less, about 600 g / mol or less, about 500 g / mol or less, about 400 g / mol or less, about 300 g / mol or less, about 200 g / mol or less, or about 100 g / mol or less. In some embodiments, the water-miscible polymer comprises an average molecular weight between about 100 g / mol and about 1000 g / mol, between about 200 g / mol and about 600 g / mol, between about 200 g / mol and about 400 g / mol, or between about 200 g / mol and about 300 g / mol. In some embodiments, the water-miscible polymer comprises an average molecular weight of about 200 g / mol or about 300 g / mol. In some embodiments, the water-miscible polymer is PEG 200 and / or PEG 300.In some embodiments, the aprotic solvent is a polar aprotic solvent, optionally a dipolar aprotic solvent. In some embodiments, the aprotic solvent is dimethyl sulfoxide (DMSO), dimethyl sulfone, diphenyl sulfone (DPS), diethylene sulfoxide, diethyl sulfone, diisopropyl sulfone, sulfolane, tetrahydrothiophene-1-monooxide, N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), or any combination thereof. In some embodiments, the aprotic solvent is sulfolane.

[0033] In some embodiments, the viscosity enhancer is at least partially soluble in the mobile phase. In some embodiments, the concentration of the viscosity enhancer is between about 1% and about 40%, between about 1% and about 35%, between about 1% and about 30%, between about 1% and about 25%, between about 1% and about 20%, between about 1% and about 15%, between about 1% and about 10%, or between about 1% and about 5% w / w. In some embodiments, the concentration of the viscosity enhancer is about 5% w / w. In some embodiments, the viscosity enhancer comprises a water-miscible polymer. In some embodiments, the water-miscible polymer comprises an average molecular weight of at least about 2000 g / mol, at least about 4000 g / mol, at least about 5000 g / mol, at least about 6000 g / mol, at least about 7000 g / mol, at least about 8000 g / mol, at least about 9000 g / mol, at least about 10000 g / mol, at least about 12000 g / mol, at least about 14000 g / mol, at least about 16000 g / mol, at least about 18000 g / mol, at least about 20000 g / mol, at least about 25000 g / mol, or at least about 30000 g / mol. In some embodiments, the water-miscible polymer comprises an average molecular weight between about 2000 g / mol and about 30000 g / mol, between about 4000 g / mol and about 20000 g / mol, between about 4000 g / mol and about 10000 g / mol, or between about 4000 g / mol and about 8000 g / mol. In some embodiments, the water-miscible polymer comprises an average molecular weight of about 4000 g / mol, about 8000 g / mol, about 10000 g / mol, or about 20000 g / mol. In some embodiments, the water-miscible polymer is an acrylic polymer, an ether polymer, an epoxy polymer, a polyethylene polymer, a polyethylene glycol polymer, a polystyrene polymer, a polyvinyl chloride polymer, a polytetrafluoroethylene polymer, a polydimethylsiloxane polymer, a polyester polymer, a poly(N-vinylpyrrolidone) polymer, a polystyrene copolymer, a polyurethane polymer, or any combination thereof. In some embodiments, the water-miscible polymer comprises a polyethylene glycol (PEG) polymer. In some embodiments, the PEG polymer is PEG 4000, PEG 8000, PEG 10000, PEG 20000, or any combination thereof. In some embodiments, the PEG polymer is PEG 8000. In some embodiments, the concentration of PEG 8000 in the composition is about 5% w / w. In some embodiments, the viscosity enhancer comprises polyvinyl alcohol (PVA).In some embodiments, the viscosity enhancer comprises sulfone or a sulfone polymer.

[0034] In some embodiments, the solubilizer is at least partially soluble in the mobile phase. In some embodiments, the solubilizer is water-soluble. In some embodiments, the concentration of the solubilizer is between about 1% and about 40%, between about 5% and about 30%, between about 10% and about 25%, or between about 10% and about 20% w / w. In some embodiments, the concentration of the solubilizer is about 15% w / w. In some embodiments, the solubilizer comprises a dissociating agent. In some embodiments, the dissociating agent is n-butanol, ethanol, guanidine salts, lithium perchlorate, lithium acetate, magnesium chloride, phenol, 2-propanol, sodium dodecyl sulfate, thiourea, urea, water-soluble urea derivatives, or any combination thereof. In some embodiments, the dissociating agent is a guanidine salt. In some embodiments, the guanidine salt is guanidine chloride, guanidine sulfate, guanidine carbonate, guanidine nitrate, guanidine isothiocyanate, guanidine thiocyanate, or any combination thereof. In some embodiments, the dissociating agent is urea and / or water-soluble urea derivatives. In some embodiments, the concentration of the urea and / or water-soluble urea derivative in the composition is about 15% w / w. In some embodiments, the water-soluble urea derivative is thiourea, hydroxyurea, dimethylurea, or any combination thereof. In some embodiments, the solubilizer comprises a buffer. In some embodiments, the buffer is MES, Bis-Tris, ADA, ACES, PIPES, MOPSO, Bis-Tris propane, BES, MOPS, TES, HEPES, DIPSO, MOBS, TAPSO, Tris, HEPPSO, POPSO, TEA, EPPS, HEPPS, Tricine, Gly-Gly, Bicine, HEPBS, TAPS, AMPD, TABS, AMPSO, CHES, CAPSO, AMP, CAPS, CABS, phosphate, maleate, glycine, citrate, formate, succinate, acetate, propionate, pyridine, piperazine, carcoate, histidine, ethanolamine, carbonate, imidazole, pyrophosphate, hydrazine, taurine (AES), borate, ammonium hydroxide, methylamine, piperidine, malate buffer, or any combination thereof. In some embodiments, the buffer comprises TAPS, HEPES, or MOPS buffer, or any combination thereof.

[0035] In some embodiments, the suspending agent comprises glycerol, the viscosity enhancer comprises PEG 8000, and the solubilizer comprises urea. In some embodiments, the concentration of glycerol is about 80% w / w, the concentration of PEG 8000 is about 5% w / w, and the concentration of urea is about 15% w / w. In some embodiments, the ratio of glycerol:PEG 8000:urea in the composition is 16:1:3 w / w. In some embodiments, the pH of the composition is between about 7 and about 8.

[0036] In some embodiments, the composition has the following viscosity: when measured at a temperature of about 15°C, between about 7000 mPa·s and about 8000 mPa·s, between about 7250 mPa·s and about 8000 mPa·s, between about 7500 mPa·s and about 8000 mPa·s, or between about 7750 mPa·s and about 8000 mPa·s; when measured at a temperature of about 20°C, between about 5000 mPa·s and about 6000 mPa·s, between about 5250 mPa·s and about 6000 mPa·s, between about 5500 mPa·s and about 6000 mPa·s, or between about 5500 mPa·s and about 5750 mPa·s; when measured at a temperature of about 25°C, between about 5500 mPa·s and about 7000 mPa·s. Between approximately 5750 mPa·s and approximately 6750 mPa·s, or between approximately 6000 mPa·s and approximately 6500 mPa·s; when measured at a temperature of approximately 30°C, between approximately 4250 mPa·s and approximately 5500 mPa·s, between approximately 4500 mPa·s and approximately 5500 mPa·s, between approximately 4750 mPa·s and approximately 5250 mPa·s, or between approximately 4750 mPa·s and approximately 5000 mPa·s; when measured at a temperature of approximately 35°C, between approximately 2000 mPa·s and approximately 3000 mPa·s, between approximately 2250 mPa·s and approximately 2750 mPa·s, or between approximately 2250 mPa·s and approximately 2500 mPa·s; when measured at a temperature of approximately 40°C, between approximately 750 mPa·s and approximately 1750 mPa·s. Between approximately 1000 mPa·s and approximately 1750 mPa·s, or between approximately 1000 mPa·s and approximately 1500 mPa·s; when measured at a temperature of approximately 45°C, between approximately 500 mPa·s and approximately 1500 mPa·s, between approximately 750 mPa·s and approximately 1250 mPa·s, or between approximately 1000 mPa·s and approximately 1250 mPa·s; when measured at a temperature of approximately 50°C, between approximately 250 mPa·s and approximately 1500 mPa·s, between approximately 500 mPa·s and approximately 1250 mPa·s, or between approximately 500 mPa·s and approximately 1000 mPa·s; when measured at a temperature of approximately 55°C, between approximately 500 mPa·s and approximately 1500 mPa·s, between approximately 750 mPa·s and approximately 1250 mPa·s. Between mPa·s, or between about 1000 mPa·s and about 1250 mPa·s;And / or when measured at a temperature of about 60°C, the viscosity is between about 100 mPa·s and about 600 mPa·s, between about 200 mPa·s and about 500 mPa·s, or between about 200 mPa·s and about 400 mPa·s. In some embodiments, a rotational viscometer is used to evaluate the viscosity of the composition. In some embodiments, the viscosity of the composition is evaluated at a shaft rotation speed of about 10 revolutions per minute (RPM).

[0037] In some embodiments, the density of the composition is between about 0.5 g / mL and about 2 g / mL, between about 1 g / mL and about 2 g / mL, between about 1 g / mL and about 1.5 g / mL, or between about 1.1 g / mL and about 1.5 g / mL. In some embodiments, the density of the composition is about 1.3 g / mL. In some embodiments, the density of the composition is assessed on an analytical balance.

[0038] In some embodiments, the mobile phase is non-aqueous or substantially non-aqueous. In some embodiments, the composition is non-aqueous or substantially non-aqueous. In some embodiments, the water content of the composition is about 1% or less. In some embodiments, the water content is assessed by Karl Fischer titration.

[0039] In some embodiments, the composition is a liquid composition.

[0040] In some embodiments, the plurality of particles comprises one or more particles configured to bind nucleic acids, peptides, lipids, carbohydrates, or small molecules. In some embodiments, the plurality of particles comprises one or more particles configured to bind DNA and / or RNA. In some embodiments, the plurality of particles comprises one or more microparticles, nanoparticles, microspheres, paramagnetic beads, magnetic beads, microbeads, nanobeads, or any combination thereof. In some embodiments, the plurality of particles comprises one or more silica beads, silica gel beads, controlled-porosity glass beads, magnetic beads, glass beads, paramagnetic beads, immunomagnetic beads, Sephadex / Sepharose beads, cellulose beads, polystyrene beads, mineral beads, crystalline particles, zircon particles, zirconium particles, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof. In some embodiments, one or more of the plurality of particles are functionalized. In some embodiments, one or more particles are surface-functionalized with carboxyl, amino, hydroxyl, silica, streptavidin, endopeptidase moiety, amine, thiol, glycol, polymer, antibody or antibody fragment, nucleic acid, oligonucleotide, peptide, polypeptide, or any combination thereof. In some embodiments, the plurality of particles comprise magnetic silica beads. In some embodiments, the plurality of particles are present in the composition at a concentration of at least about 0.5%, at least about 1%, at least about 2.5%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 30% by weight / volume (w / v). In some embodiments, the plurality of particles are present in the composition at a concentration between about 0.5% and about 30% w / v, between about 1% and about 25% w / v, between about 2.5% and about 20% w / v, or between about 5% and about 15% w / v. In some embodiments, the plurality of particles are present in the composition at a concentration of about 10% w / v.

[0041] In some embodiments, the composition enhances the stability of particles in a plurality of particles. In some embodiments, the composition enhances the stability of particles in a plurality of particles compared to corresponding particles in an aqueous solution. In some embodiments, the plurality of particles in the composition are stable for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months. In some embodiments, particle stability is assessed based on particle integrity, particle aggregation, and / or retention of ligand binding capacity. In some implementations, compared to a baseline, the particles among the plurality of particles maintain at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 90%, at least about 95%, at least about 95%, or at least about 99% ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% of the ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 8 months, at least about 9 months, at least about 95%, or at least about 99% of the ligand binding capacity. In some embodiments, the composition enhances ligand binding of the particles in the plurality of particles by at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% compared to corresponding particles in an aqueous solution. In some embodiments, the plurality of particles comprises particles capable of binding nucleic acid ligands. In some embodiments, the stability of the particles is assessed based on nucleic acid ligand binding capacity compared to a baseline and / or to corresponding particles in an aqueous solution. In some embodiments, the nucleic acid ligand comprises DNA and / or RNA. In some embodiments, the plurality of particles comprises silica particles. In some embodiments, the plurality of particles comprises magnetic silica particles.In some implementations, compared to a baseline, the particles among the plurality of particles maintain at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 95%, or at least about 99% of their nucleic acid ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% of their nucleic acid ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months. In some embodiments, the composition enhances the binding of nucleic acid ligands to particles in a plurality of particles by at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% compared to corresponding particles in an aqueous solution. In some embodiments, particle stability is evaluated at room temperature. In some embodiments, particle stability is evaluated at a temperature between about 20°C and about 30°C. In some embodiments, particle stability is evaluated at a temperature of about 25°C. In some embodiments, particle stability is evaluated under normal atmospheric conditions, under low oxygen conditions, or in nitrogen. In some embodiments, the composition is capable of adhering to a polypropylene surface. In some embodiments, the composition has microbiological stability for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months.

[0042] In some embodiments, the composition further comprises agents such as antioxidants, reducing agents, chelating agents, or any combination thereof. In some embodiments, the composition does not contain antimicrobial agents. In some embodiments, the composition contains less than about 10% surfactant or detergent. In some embodiments, the composition does not contain surfactant or detergent.

[0043] On the other hand, this document provides compositions comprising multiple particles produced by any of the methods for preparing compositions provided herein.

[0044] On the other hand, this document provides a method for separating an analyte from a sample, comprising: (a) providing a sample containing (or suspected to contain) an analyte; (b) mixing the sample with a composition comprising multiple particles provided herein or a composition comprising multiple particles produced by the methods provided herein to produce a mixture of the sample and the composition, thereby binding the analyte (if present) to one or more of the multiple particles; and (c) separating the multiple particles from the mixture. In some embodiments, the method further includes eluting the analyte bound to one or more of the multiple particles and optionally separating the multiple particles from the eluted analyte. In some embodiments, the method further includes separating or recovering the eluted analyte. In some embodiments, the analyte is a nucleic acid, peptide, lipid, carbohydrate, or small molecule. In some embodiments, the analyte is DNA and / or RNA. In some embodiments, the multiple particles comprise one or more particles configured to bind DNA and / or RNA. In some embodiments, the multiple particles comprise one or more microparticles, nanoparticles, microspheres, paramagnetic beads, magnetic beads, microbeads, nanobeads, or any combination thereof. In some embodiments, the plurality of particles comprises one or more silica beads, silica gel beads, glass beads with controllable porosity, magnetic beads, glass beads, paramagnetic beads, immunomagnetic beads, Sephadex / Sepharose beads, cellulose beads, polystyrene beads, mineral beads, crystalline particles, zircon particles, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof. In some embodiments, the plurality of particles are functionalized, optionally wherein one or more of the particles are surface functionalized with carboxyl, amino, hydroxyl, silica, streptavidin, endopeptidase moiety, amine, thiol, glycol, polymer, antibody or antibody fragment, nucleic acid, oligonucleotide, peptide, polypeptide, or any combination thereof. In some embodiments, the plurality of particles comprises silica beads, optionally magnetic silica beads, and further optionally wherein the analyte is DNA and / or RNA. In some embodiments, the sample is or is derived from tissue, primary or cultured cells or cell lines, cell supernatant, cell lysate, platelets, serum, plasma, vitreous fluid, lymph, synovial fluid, follicular fluid, semen, amniotic fluid, breast milk, whole blood, blood-derived cells, urine, cerebrospinal fluid, saliva, sputum, tears, sweat, mucus, tumor lysate, tissue culture medium, tissue extract, homogenate, tumor tissue, cell extract, or combinations thereof. In some embodiments, the sample is a liquid biopsy sample, optionally wherein the liquid biopsy sample is a blood or plasma sample.In some embodiments, the sample is a liquid biopsy sample, and the analyte is cell-free DNA or cell-free RNA. In some embodiments, the sample is or is derived from a nasal swab, oral swab, cervical swab, ear swab, eye swab, vaginal swab, penile swab, rectal swab, throat swab, urethral swab, vulvar swab, wound swab, or skin swab. In some embodiments, the sample is or is derived from environmental samples, such as water samples, soil samples, surface samples, air samples, rock or mineral samples, plant samples, sediment samples, etc.; food samples, such as plant samples, meat samples, dairy product samples, plant or animal-derived product samples, food additive or ingredient samples, etc.; or any other type of sample that may contain the analyte of interest.

[0045] On the other hand, this document provides a method for cell lysis, comprising: (a) providing a sample containing a plurality of cells; (b) mixing the sample with a composition containing a plurality of particles provided herein or a composition containing a plurality of particles produced by the methods provided herein, thereby producing a mixture of the sample and the composition; and (c) stirring the mixture to lyse one or more cells among the plurality of cells. In some embodiments, the method further includes separating the plurality of particles from the mixture. In some embodiments, the one or more cells comprise one or more prokaryotic cells and / or one or more eukaryotic cells. In some embodiments, the one or more cells comprise one or more animal cells, plant cells, mammalian cells, bacterial cells, archaea cells, fungal cells, protozoan cells, algal cells, or any combination thereof. In some embodiments, the plurality of particles comprise one or more mineral beads, crystalline particles, zircon particles, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof. In some implementations, the method is carried out on microfluidic devices and / or automated or robotic liquid handling systems.

[0046] On the other hand, this document provides a kit comprising a composition provided herein or a composition produced by a method provided herein. In some embodiments, the kit further comprises instructions for isolating one or more analytes from a sample using the kit or a composition in the kit, optionally wherein the instructions are for isolating one or more analytes from a sample according to a method provided herein. In some embodiments, the kit further comprises instructions for lysing one or more cells from a sample using the kit or a composition in the kit, optionally wherein the instructions are for lysing one or more cells according to a method provided herein.

[0047] On the other hand, this document provides a microfluidic device comprising the compositions provided herein or compositions produced by the methods provided herein.

[0048] It should be understood that one, some, or all of the features of the various embodiments described herein can be combined to form other embodiments of the invention. These and other aspects of the invention will become apparent to those skilled in the art. These and other embodiments of the invention are further described in the following detailed description. Attached Figure Description

[0049] Figure 1 This is a box plot showing the RNA separation efficiency of silica magnetic beads stored in Formulation K (see Examples 2-3 herein) at room temperature and under normal atmospheric conditions over the indicated time periods (from 3 to 15 months). Separation efficiency is provided as a percentage of RNA separation efficiency relative to beads stored in aqueous solution ("wet beads", set as 100%). Detailed Implementation

[0050] This disclosure generally relates to compositions comprising multiple particles, methods for preparing such compositions, and related uses, kits, and articles thereof.

[0051] Particles, such as beads, are important tools in various fields, including research (e.g., molecular biology research), diagnostics, medicine, and industrial applications. This disclosure provides compositions that support and / or enhance particle stability and functionality, and facilitate particle handling and storage, including long-term storage under normal environmental conditions. This disclosure also provides methods for preparing particle compositions, certain uses of such compositions, and related kits and articles.

[0052] I. Definition

[0053] As used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural references unless the context clearly indicates otherwise.

[0054] Unless otherwise stated, the terms “comprising,” “having,” “including,” and “containing” should be interpreted as open-ended terms (i.e., meaning “including but not limited to”).

[0055] The descriptions of numerical ranges in this document are intended only as a concise way of referring to each individual value falling within that range, unless otherwise stated herein, and each individual value is incorporated into the specification as if it were described separately herein. For example, if the range 10–15 is disclosed, then 11, 12, 13, and 14 are also disclosed.

[0056] The reference to “about” in this document for a numerical value or parameter refers to the general range of error for each value that is readily known to those skilled in the art. For example, the reference to “about” in this document includes (and describes) an aspect relating to the numerical value or parameter itself, as well as the variation (range of error) around the numerical value or parameter, for example, within 0-10% (e.g., X ± 10%). In a specific instance, when the term “about” is used in the context of compositions containing amounts of ingredients, these compositions may contain said amount of ingredients, the variation (range of error) of which is, for example, within 0-10% (e.g., X ± 10%) around the stated value. The reference to “about” in this document includes (and describes) an aspect relating to the numerical value or parameter itself. For example, a description of “about X” includes a description of “X”.

[0057] The use of any and all instances or exemplary language (e.g., "such as," "exemplary," or "for example") provided herein is intended only to better illustrate implementations of this disclosure and does not constitute a limitation on the scope of this disclosure unless otherwise stated. No language in the specification should be construed as indicating that any unclaimed element is essential to the practice of implementations of this disclosure. Unless otherwise indicated herein or where the context clearly contradicts it, all methods described herein may be performed in any suitable order.

[0058] II. The compositions disclosed herein

[0059] Certain aspects of this disclosure relate to compositions comprising one or more particles. As described in more detail below, compositions of this disclosure may have one, more, or all of the following properties: low or no water content (e.g., may be non-aqueous or substantially non-aqueous), adhesion to surfaces (e.g., plastic or glass surfaces), high viscosity, high density, sustained and / or enhanced particle stability and / or particle functionality, sustained and / or enhanced particle ligand binding, and / or microbiological stability.

[0060] In some embodiments, the compositions of this disclosure may comprise one or more particles, and any two or all three of the following: (a) a mobile phase, (b) a viscosity enhancer, and (c) a solubilizer. In some embodiments, the compositions of this disclosure comprise said one or more particles, a mobile phase, and a viscosity enhancer. In some embodiments, the compositions of this disclosure comprise said one or more particles, a mobile phase, and a solubilizer. In some embodiments, the compositions of this disclosure comprise said one or more particles, a viscosity enhancer, and a solubilizer. In some embodiments, the compositions of this disclosure comprise said one or more particles, a mobile phase, a viscosity enhancer, and a solubilizer.

[0061] The compositions disclosed herein may be liquid compositions. In some cases, the compositions disclosed herein have relatively high viscosity and / or density. Therefore, in some embodiments, the compositions disclosed herein may be pastes, creams, or gels. In some embodiments, the compositions disclosed herein are non-aqueous or substantially non-aqueous.

[0062] a. Mobile phase

[0063] In some embodiments, the compositions of this disclosure comprise a mobile phase. The mobile phase is typically a fluid that can be used to suspend the components of the composition in a solution.

[0064] In some embodiments, the compositions of this disclosure comprise a mobile phase at a concentration of at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% (w / w) by weight. In some embodiments, the compositions comprise a mobile phase at a concentration between about 50% and about 99%, between about 60% and about 99%, between about 60% and about 95%, between about 65% and about 90%, between about 70% and about 90%, between about 75% and about 90%, or between about 80% and about 90% (w / w), including any value within each of the stated ranges. In some embodiments, the compositions of this disclosure comprise a mobile phase at a concentration of about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, or about 95% (w / w). In some embodiments, the compositions of this disclosure comprise a mobile phase at a concentration of about 80% w / w.

[0065] Any suitable mobile phase can be used in the compositions of this disclosure. In some embodiments, the mobile phase may be, for example, a solvent, detergent, water, and / or a suspending agent. In some embodiments, the mobile phase is non-aqueous or substantially non-aqueous. In some embodiments, the mobile phase may be miscible with water or water-soluble.

[0066] In some embodiments, the mobile phase of the compositions of this disclosure comprises one or more suspending agents. Suspension agents are typically excipients that help keep components in the composition (e.g., particles and other components) suspended and / or dispersed in the composition, and can inhibit or reduce aggregation, agglomeration, and / or sedimentation. Any suitable suspending agent known in the art may be used in the compositions of this disclosure. Exemplary suspending agents that may be used include, but are not limited to, sugar alcohols, glycols, water-miscible polymers, aprotic solvents, and any combination thereof.

[0067] In some embodiments, the suspending agent in the compositions of this disclosure comprises a sugar alcohol. Any suitable sugar alcohol known in the art may be used in the compositions of this disclosure. Exemplary sugar alcohols that may be used include, but are not limited to, glycerol, sorbitol, erythritol, threitol, arabinitol, xylitol, ribitol, mannitol, galactitol, fucitol, idoterol, inositol, heptaheptaol, isomaltitol, maltitol, lactitol, maltotriol, maltotetratitol, polyglycol, and any combination thereof. In some embodiments, the sugar alcohol comprises glycerol. In some embodiments, the concentration of the sugar alcohol (e.g., glycerol) in the composition is at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% w / w. In some embodiments, the concentration of the sugar alcohol (e.g., glycerol) in the composition is between about 50% and about 99%, between about 60% and about 99%, between about 60% and about 95%, between about 65% and about 90%, between about 70% and about 90%, between about 75% and about 90%, or between about 80% and about 90% (w / w), including any value within each of the stated ranges. In some embodiments, the concentration of the sugar alcohol (e.g., glycerol) in the composition is about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, or about 95% w / w. In some embodiments, the sugar alcohol (e.g., glycerol) is present in the composition at a concentration of about 80% w / w. In some embodiments, the sugar alcohol comprises glycerol at a concentration of about 80% w / w in the composition. In some embodiments, the sugar alcohol (e.g., glycerol) is present in the composition at a concentration of about 78% w / w. In some embodiments, the sugar alcohol comprises glycerol at a concentration of about 78% w / w in the composition.

[0068] In some embodiments, the suspending agent in the compositions of this disclosure comprises a diol. Any suitable diol known in the art may be used in the compositions of this disclosure. Exemplary diols that may be used include, but are not limited to, diethylene glycol, ethylene glycol, hexanediol, propylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, glycol ethers, and any combination thereof. In some embodiments, the suspending agent in the compositions of this disclosure comprises propylene glycol. In some embodiments, the concentration of the diol (e.g., propylene glycol) in the composition is at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% w / w. In some embodiments, the concentration of the diol (e.g., propylene glycol) in the composition is between about 50% and about 99%, between about 60% and about 99%, between about 60% and about 95%, between about 65% and about 90%, between about 70% and about 90%, between about 75% and about 90%, or between about 80% and about 90% (w / w), including any value within each of the said ranges. In some embodiments, the concentration of the diol (e.g., propylene glycol) in the composition is about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, or about 95% w / w. In some embodiments, the concentration of the diol (e.g., propylene glycol) in the composition is about 80% w / w.

[0069] In some embodiments, the suspending agent in the compositions of this disclosure comprises a water-miscible polymer. Any suitable water-miscible polymer known in the art may be used in the compositions of this disclosure. Exemplary water-miscible polymers that may be used include, but are not limited to, acrylic polymers, ether polymers, epoxy polymers, polyethylene polymers, polyethylene glycol polymers, polystyrene polymers, polyvinyl chloride polymers, polytetrafluoroethylene polymers, polydimethylsiloxane polymers, polyester polymers, poly(N-vinylpyrrolidone) polymers, polystyrene copolymers, polyvinyl alcohol (PVA), polyurethane polymers, and any combination thereof. In some embodiments, the water-miscible polymer comprises a polyethylene glycol (PEG) polymer. In some embodiments, the average molecular weight of the water-miscible polymer is about 1000 g / mol or less, about 900 g / mol or less, about 800 g / mol or less, about 700 g / mol or less, about 600 g / mol or less, about 500 g / mol or less, about 400 g / mol or less, about 300 g / mol or less, about 200 g / mol or less, or about 100 g / mol or less. In some embodiments, the average molecular weight of the water-miscible polymer is about 300 g / mol or less, about 200 g / mol or less, or about 100 g / mol or less. In some embodiments, the average molecular weight of the water-miscible polymer is between about 100 g / mol and about 2000 g / mol, between about 100 g / mol and about 1000 g / mol, between about 200 g / mol and about 600 g / mol, between about 200 g / mol and about 400 g / mol, or between about 200 g / mol and about 300 g / mol, including any value within each of the said ranges. In some embodiments, the average molecular weight of the water-miscible polymer is about 100 g / mol, about 200 g / mol, about 300 g / mol, about 400 g / mol, about 500 g / mol, about 600 g / mol, about 700 g / mol, about 800 g / mol, about 900 g / mol, or about 1000 g / mol. In some embodiments, the average molecular weight of the water-miscible polymer is about 200 g / mol or about 300 g / mol. In some embodiments, the water-miscible polymer is a PEG polymer, such as PEG 200, PEG 300, PEG 400, PEG 600, or PEG 1000. In some embodiments, the water-miscible polymer is PEG 200 and / or PEG 300.In some embodiments, the concentration of the water-miscible polymer (e.g., a PEG polymer, such as PEG 200 and / or PEG 300) in the composition is at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% w / w. In some embodiments, the concentration of the water-miscible polymer (e.g., a PEG polymer, such as PEG 200 and / or PEG 300) in the composition is between about 50% and about 99%, between about 60% and about 99%, between about 60% and about 95%, between about 65% and about 90%, between about 70% and about 90%, between about 75% and about 90%, or between about 80% and about 90% (w / w), including any value within each of the stated ranges. In some embodiments, the concentration of the water-miscible polymer (e.g., a PEG polymer, such as PEG 200 and / or PEG 300) in the composition is about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, or about 95% w / w. In some embodiments, the concentration of the water-miscible polymer (e.g., a PEG polymer, such as PEG 200 and / or PEG 300) in the composition is about 80% w / w.

[0070] In some embodiments, the suspending agent in the compositions of this disclosure comprises an aprotic solvent. In some embodiments, the aprotic solvent is a polar aprotic solvent. In some embodiments, the aprotic solvent is a dipolar aprotic solvent. Any suitable aprotic solvent known in the art may be used in the compositions of this disclosure. Exemplary aprotic solvents that may be used include, but are not limited to, dimethyl sulfoxide (DMSO), dimethyl sulfone, diphenyl sulfone (DPS), diethylene sulfoxide, diethyl sulfone, diisopropyl sulfone, sulfolane, tetrahydrothiophene-1-monooxide, N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), and any combination thereof. In some embodiments, the aprotic solvent comprises sulfolane. In some embodiments, the concentration of the aprotic solvent (e.g., sulfolane) in the composition is at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% w / w. In some embodiments, the concentration of the aprotic solvent (e.g., sulfolane) in the composition is between about 50% and about 99%, between about 60% and about 99%, between about 60% and about 95%, between about 65% and about 90%, between about 70% and about 90%, between about 75% and about 90%, or between about 80% and about 90% (w / w), including any value within each of the stated ranges. In some embodiments, the concentration of the aprotic solvent (e.g., sulfolane) in the composition is about 70%, about 71%, about 72%, about 73%, about 74%, about 75%, about 76%, about 77%, about 78%, about 79%, about 80%, about 81%, about 82%, about 83%, about 84%, about 85%, about 86%, about 87%, about 88%, about 89%, about 90%, about 91%, about 92%, about 93%, about 94%, or about 95% w / w. In some embodiments, the concentration of the aprotic solvent (e.g., sulfolane) in the composition is about 80% w / w.

[0071] b. Viscosity enhancer

[0072] In some embodiments, the compositions of this disclosure include viscosity enhancers. Such agents can be used to increase the viscosity of the composition and may include, for example, polymers, thickeners, texturers, crosslinking agents, gelling agents, and hardeners.

[0073] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve any of the following viscosities in the final composition: at least about 7000 mPa·s, at least about 7100 mPa·s, at least about 7200 mPa·s, at least about 7300 mPa·s, at least about 7400 mPa·s, at least about 7500 mPa·s, at least about 7600 mPa·s, at least about 7700 mPa·s, at least about 7800 mPa·s, at least about 7900 mPa·s, or at least about 8000 mPa·s when measured at about 15°C; or between about 7000 mPa·s and about 8000 mPa·s, between about 7250 mPa·s and about 8000 mPa·s, between about 7500 mPa·s and about 8000 mPa·s, or between about 7750 mPa·s and about 8000 mPa·s when measured at about 15°C. The values ​​are between mPa·s, including any value within each of the ranges.

[0074] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve any of the following viscosities in the final composition: at least about 5000 mPa·s, at least about 5100 mPa·s, at least about 5200 mPa·s, at least about 5300 mPa·s, at least about 5400 mPa·s, at least about 5500 mPa·s, at least about 5600 mPa·s, at least about 5700 mPa·s, at least about 5800 mPa·s, at least about 5900 mPa·s, or at least about 6000 mPa·s when measured at about 20°C; or between about 5000 mPa·s and about 6000 mPa·s, between about 5250 mPa·s and about 6000 mPa·s, between about 5500 mPa·s and about 6000 mPa·s, or between about 5500 mPa·s and about 5750 mPa·s when measured at about 20°C. The values ​​are between mPa·s, including any value within each of the ranges.

[0075] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve a final composition viscosity of any of the following: at least about 5500 mPa·s, at least about 5600 mPa·s, at least about 5700 mPa·s, at least about 5800 mPa·s, at least about 5900 mPa·s, at least about 6000 mPa·s, at least about 6100 mPa·s, at least about 6200 mPa·s, at least about 6300 mPa·s, at least about 6400 mPa·s, at least about 6500 mPa·s, at least about 6600 mPa·s, at least about 6700 mPa·s, at least about 6800 mPa·s, at least about 6900 mPa·s, or at least about 7000 mPa·s when measured at about 25°C; or at least between about 5500 mPa·s and about 7000 mPa·s when measured at about 25°C. Between mPa·s, between about 5750 mPa·s and about 6750 mPa·s, or between about 6000 mPa·s and about 6500 mPa·s, including any value within each of the stated ranges.

[0076] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve a final composition viscosity of any of the following: at least about 4200 mPa·s, at least about 4300 mPa·s, at least about 4400 mPa·s, at least about 4500 mPa·s, at least about 4600 mPa·s, at least about 4700 mPa·s, at least about 4800 mPa·s, at least about 4900 mPa·s, at least about 5000 mPa·s, at least about 5100 mPa·s, at least about 5200 mPa·s, at least about 5300 mPa·s, at least about 5400 mPa·s, or at least about 5500 mPa·s when measured at about 30°C; or between about 4250 mPa·s and about 5500 mPa·s when measured at about 30°C. Between mPa·s, between about 4750 mPa·s and about 5250 mPa·s, or between about 4750 mPa·s and about 5000 mPa·s, including any value in each of the said ranges.

[0077] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve any of the following viscosities when measured at a temperature of about 35°C: at least about 2000 mPa·s, at least about 2100 mPa·s, at least about 2200 mPa·s, at least about 2300 mPa·s, at least about 2400 mPa·s, at least about 2500 mPa·s, at least about 2600 mPa·s, at least about 2700 mPa·s, at least about 2800 mPa·s, at least about 2900 mPa·s, or at least about 3000 mPa·s; or when measured at a temperature of about 35°C: between about 2000 mPa·s and about 3000 mPa·s, between about 2250 mPa·s and about 2750 mPa·s, or between about 2250 mPa·s and about 2500 mPa·s, including any value within each of the aforementioned ranges.

[0078] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve any of the following viscosities when measured at a temperature of about 40°C: at least about 750 mPa·s, at least about 850 mPa·s, at least about 950 mPa·s, at least about 1050 mPa·s, at least about 1150 mPa·s, at least about 1250 mPa·s, at least about 1350 mPa·s, at least about 1450 mPa·s, at least about 1550 mPa·s, at least about 1650 mPa·s, or at least about 1750 mPa·s; or when measured at a temperature of about 40°C: between about 750 mPa·s and about 1750 mPa·s, between about 1000 mPa·s and about 1750 mPa·s, or between about 1000 mPa·s and about 1500 mPa·s, including any value within each of the stated ranges.

[0079] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve any of the following viscosities when measured at a temperature of about 45°C: at least about 500 mPa·s, at least about 600 mPa·s, at least about 700 mPa·s, at least about 800 mPa·s, at least about 900 mPa·s, at least about 1000 mPa·s, at least about 1100 mPa·s, at least about 1200 mPa·s, at least about 1300 mPa·s, at least about 1400 mPa·s, or at least about 1500 mPa·s; or when measured at a temperature of about 45°C: between about 500 mPa·s and about 1500 mPa·s, between about 750 mPa·s and about 1250 mPa·s, or between about 1000 mPa·s and about 1250 mPa·s, including any value within each of the stated ranges.

[0080] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve any of the following viscosities in the final composition: at least about 250 mPa·s, at least about 350 mPa·s, at least about 450 mPa·s, at least about 550 mPa·s, at least about 650 mPa·s, at least about 750 mPa·s, at least about 850 mPa·s, at least about 950 mPa·s, at least about 1050 mPa·s, at least about 1150 mPa·s, at least about 1250 mPa·s, at least about 1350 mPa·s, at least about 1450 mPa·s, or at least about 1550 mPa·s when measured at about 50°C; or between about 250 mPa·s and about 1500 mPa·s, between about 500 mPa·s and about 1250 mPa·s, or between about 500 mPa·s and about 1000 mPa·s when measured at about 50°C. The values ​​are between mPa·s, including any value within each of the ranges.

[0081] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve any of the following viscosities when measured at a temperature of about 55°C: at least about 500 mPa·s, at least about 600 mPa·s, at least about 700 mPa·s, at least about 800 mPa·s, at least about 900 mPa·s, at least about 1000 mPa·s, at least about 1100 mPa·s, at least about 1200 mPa·s, at least about 1300 mPa·s, at least about 1400 mPa·s, or at least about 1500 mPa·s; or when measured at a temperature of about 55°C: between about 500 mPa·s and about 1500 mPa·s, between about 750 mPa·s and about 1250 mPa·s, or between about 1000 mPa·s and about 1250 mPa·s, including any value within each of the stated ranges.

[0082] In some embodiments, the compositions of this disclosure comprise one or more viscosity enhancers in an amount sufficient to achieve any of the following viscosities when measured at a temperature of about 60°C: at least about 100 mPa·s, at least about 150 mPa·s, at least about 200 mPa·s, at least about 250 mPa·s, at least about 300 mPa·s, at least about 350 mPa·s, at least about 400 mPa·s, at least about 450 mPa·s, at least about 500 mPa·s, at least about 550 mPa·s, or at least about 600 mPa·s; or when measured at a temperature of about 60°C: between about 100 mPa·s and about 600 mPa·s, between about 200 mPa·s and about 500 mPa·s, or between about 200 mPa·s and about 400 mPa·s, including any value within each of the stated ranges.

[0083] The viscosity of the compositions disclosed herein can be evaluated using any suitable technique known in the art, such as a capillary viscometer, viscosity cup, Zahn cup, falling ball viscometer, vibration viscometer, rotational viscometer, or consistency meter. In some embodiments, a rotational viscometer is used to evaluate the viscosity of the compositions disclosed herein. In some cases, the viscosity can be evaluated at a spindle speed of about 10 revolutions per minute (RPM).

[0084] In some embodiments, the compositions of this disclosure comprise a viscosity enhancer at a concentration of at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50% (w / w). In some embodiments, the compositions of this disclosure comprise a viscosity enhancer at a concentration between about 1% and about 50%, between about 1% and about 40%, between about 1% and about 35%, between about 1% and about 30%, between about 1% and about 25%, between about 1% and about 20%, between about 1% and about 15%, between about 1% and about 10%, or between about 1% and about 5% (w / w), including any value within each of these ranges. In some embodiments, the compositions of this disclosure comprise a viscosity enhancer at a concentration of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% w / w. In some embodiments, the concentration of the viscosity enhancer is about 5% w / w.

[0085] Any suitable viscosity enhancer can be used in the compositions of this disclosure. In some embodiments, the viscosity enhancer of this disclosure may be, for example, a polymer, thickener, texturer, gelling agent, crosslinking agent, hardener, or combination thereof. In some embodiments, the viscosity enhancer is at least partially soluble in the mobile phase of the composition.

[0086] In some embodiments, the viscosity enhancer comprises a water-miscible polymer. Any suitable water-miscible polymer known in the art may be used in the compositions of this disclosure. Exemplary water-miscible polymers that may be used include, but are not limited to, acrylic polymers, ether polymers, epoxy polymers, polyethylene polymers, polyethylene glycol polymers, polystyrene polymers, polyvinyl chloride polymers, polytetrafluoroethylene polymers, polydimethylsiloxane polymers, polyester polymers, poly(N-vinylpyrrolidone) polymers, polystyrene copolymers, polyvinyl alcohol (PVA), polyurethane polymers, and any combination thereof. In some embodiments, the water-miscible polymer in the compositions of this disclosure includes a polyethylene glycol (PEG) polymer.

[0087] In some embodiments, the water-miscible polymer has an average molecular weight of at least about 1000 g / mol, at least about 2000 g / mol, at least about 3000 g / mol, at least about 4000 g / mol, at least about 5000 g / mol, at least about 6000 g / mol, at least about 7000 g / mol, at least about 8000 g / mol, at least about 9000 g / mol, at least about 10000 g / mol, at least about 11000 g / mol, at least about 12000 g / mol, at least about 13000 g / mol, at least about 14000 g / mol, at least about 15000 g / mol, at least about 16000 g / mol, at least about 17000 g / mol, at least about 18000 g / mol, at least about 19000 g / mol, at least about 20000 g / mol, at least about 21000 g / mol, at least about 22000 g / mol. The molecular weight is at least about 23,000 g / mol, at least about 24,000 g / mol, at least about 25,000 g / mol, at least about 26,000 g / mol, at least about 27,000 g / mol, at least about 28,000 g / mol, at least about 29,000 g / mol, or at least about 30,000 g / mol. In some embodiments, the water-miscible polymer has an average molecular weight between about 1,000 g / mol and about 30,000 g / mol, between about 2,000 g / mol and about 30,000 g / mol, between about 4,000 g / mol and about 20,000 g / mol, between about 4,000 g / mol and about 10,000 g / mol, or between about 4,000 g / mol and about 8,000 g / mol, including any value within the range. In some cases, the water-miscible polymer has an average molecular weight of about 4000 g / mol, about 8000 g / mol, about 10000 g / mol, or about 20000 g / mol. In some embodiments, the water-miscible polymer is a PEG polymer, such as PEG 4000, PEG 8000, PEG 10000, or PEG 20000 and any combination thereof. In some embodiments, the water-miscible polymer is PEG 8000. In some embodiments, the water-miscible polymer is PVA.

[0088] In some embodiments, the concentration of the water-miscible polymer (e.g., PEG polymers such as PEG 4000, PEG8000, PEG 10000, PEG 20000, PVA, or combinations thereof) is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50% w / w. In some embodiments, the concentration of the water-miscible polymer (e.g., PEG polymers such as PEG 4000, PEG 8000, PEG 10000, PEG 20000, PVA, or combinations thereof) is between about 1% and about 50%, between about 1% and about 40%, between about 1% and about 35%, between about 1% and about 30%, between about 1% and about 25%, between about 1% and about 20%, between about 1% and about 15%, between about 1% and about 10%, or between about 1% and about 5% (w / w), including any value within each of the stated ranges. In some embodiments, the concentration of the water-miscible polymer (e.g., PEG polymers such as PEG 4000, PEG 8000, PEG 10000, PEG 20000, PVA, or combinations thereof) is about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% w / w. In some embodiments, the water-miscible polymer comprises PEG 8000 at a concentration of about 5% w / w in the composition. In some embodiments, the water-miscible polymer comprises PEG 8000 at a concentration of about 7% w / w in the composition. In some embodiments, the water-miscible polymer comprises PEG 10000 at a concentration of about 5% w / w in the composition. In some embodiments, the water-miscible polymer comprises PEG 10000 at a concentration of about 7% w / w in the composition.

[0089] In some embodiments, the viscosity enhancer comprises a sulfone or a sulfone polymer. In some embodiments, the concentration of the sulfone or sulfone polymer is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50% w / w. In some embodiments, the concentration of the sulfone or sulfone polymer is between about 1% and about 50%, between about 1% and about 40%, between about 1% and about 35%, between about 1% and about 30%, between about 1% and about 25%, between about 1% and about 20%, between about 1% and about 15%, between about 1% and about 10%, or between about 1% and about 5% (w / w), including any value within each of these ranges. In some embodiments, the concentration of the sulfone or sulfone polymer is about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, or about 10% w / w.

[0090] c. Solubilizer

[0091] In some embodiments, the compositions of this disclosure comprise one or more solubilizers. Solubilizers can increase the solubility of the composition components and / or prevent aggregation or clumping, for example, by disrupting intermolecular interactions (e.g., disulfide bonds, hydrogen bonds, van der Waals forces, ionic interactions, hydrophobic interactions, hydrophilic interactions, etc.).

[0092] In some embodiments, the compositions of this disclosure comprise one or more solubilizers at a concentration of at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50% w / w. In some embodiments, the compositions of this disclosure comprise one or more solubilizers at a concentration between about 1% and about 50%, between about 5% and about 30%, between about 10% and about 25%, or between about 10% and about 20% (w / w), including any value within each of these ranges. In some embodiments, the compositions of this disclosure comprise one or more solubilizers at a concentration of about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% w / w. In some embodiments, the compositions disclosed herein contain one or more solubilizers at a concentration of about 15% w / w.

[0093] Any suitable solubilizer may be used in the compositions of this disclosure. Exemplary solubilizers that may be used include, but are not limited to, reducing agents, dissociating agents, surfactants, buffers, and salts. In some embodiments, the solubilizer used in the compositions of this disclosure is at least partially soluble in the mobile phase of the composition and / or water-soluble or miscible with water.

[0094] In some embodiments, the compositions of this disclosure include a liquid-dissolving agent as a solubilizing component. In some embodiments, the liquid-dissolving agent is at least partially soluble in the mobile phase and / or water-soluble or miscible with water. Any suitable liquid-dissolving agent known in the art may be used in the compositions of this disclosure. Exemplary liquid-dissolving agents that may be used include, but are not limited to, n-butanol, ethanol, guanidine salts, lithium perchlorate, lithium acetate, magnesium chloride, phenol, 2-propanol, sodium dodecyl sulfate, thiourea, urea, water-soluble urea derivatives, and any combination thereof. In some embodiments, the liquid-dissolving agent in the composition includes urea or a water-soluble urea derivative (e.g., any one of thiourea, hydroxyurea, dimethylurea, and any combination thereof). In other embodiments, the liquid-dissolving agent in the composition includes a guanidine salt (e.g., any one of guanidine chloride, guanidine sulfate, guanidine carbonate, guanidine nitrate, guanidine isothiocyanate, guanidine thiocyanate, and any combination thereof). In some embodiments, the concentration of the dissociating agent (e.g., urea, urea derivatives, and / or guanidine salts) in the composition is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50% w / w. In some embodiments, the concentration of the dissociating agent (e.g., urea, urea derivatives, and / or guanidine salts) in the composition is between about 1% and about 50%, between about 1% and about 40%, between about 5% and about 30%, between about 10% and about 25%, or between about 10% and about 20% (w / w), including any value within each of the aforementioned ranges. In some embodiments, the concentration of the dissociating agent (e.g., urea, urea derivatives, and / or guanidine salts) in the composition is about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% w / w. In some embodiments, the concentration of the dissociating agent (e.g., urea, urea derivatives, and / or guanidine salts) in the composition is about 15% w / w. In some embodiments, the dissociating agent comprises urea at a concentration of about 15% w / w in the composition.

[0095] In some embodiments, the compositions of this disclosure include a buffer as a solubilizing component. In some embodiments, the buffer is at least partially soluble in the mobile phase and / or water-soluble or miscible with water. Any suitable buffer known in the art may be used in the compositions of this disclosure. Exemplary buffers that can be used include, but are not limited to, MES, Bis-Tris, ADA, ACES, PIPES, MOPSO, Bis-Tris propane, BES, MOPS, TES, HEPES, DIPSO, MOBS, TAPSO, Tris, HEPPSO, POPSO, TEA, EPPS, HEPPS, Tricine, Gly-Gly, Bicine, HEPBS, TAPS, AMPD, TABS, AMPSO, CHES, CAPSO, AMP, CAPS, CABS, phosphates, maleates, glycine, citrate, formate, succinate, acetate, propionate, pyridine, piperazine, carcolate, histidine, ethanolamine, carbonates, imidazole, pyrophosphate, hydrazine, taurine (AES), borates, ammonium hydroxide, methylamine, piperidine, or malate buffers, and any combination thereof. In some embodiments, the buffer in the composition includes TAPS, HEPES, or MOPS buffers, or any combination thereof. In some embodiments, the concentration of the buffer (e.g., TAPS, HEPES, or MOPS buffer, or any combination thereof) in the composition is at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, or at least about 50% w / w. In some embodiments, the concentration of the buffer (e.g., TAPS, HEPES, or MOPS buffer, or any combination thereof) in the composition is between about 1% and about 50%, between about 1% and about 40%, between about 5% and about 30%, between about 10% and about 25%, or between about 10% and about 20% (w / w), including any value within each of the stated ranges. In some embodiments, the buffer (e.g., TAPS, HEPES, or MOPS buffer, or any combination thereof) is present in the composition at a concentration of about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% w / w. In some embodiments, the buffer (e.g., TAPS, HEPES, or MOPS buffer, or any combination thereof) is present in the composition at a concentration of about 15% w / w.

[0096] d. Particles

[0097] The compositions disclosed herein are suitable for use with any type of particles known in the art, such as any particles that would benefit from any or all of the properties of the compositions disclosed herein, as described herein (e.g., low or no water content, surface adhesion, high viscosity, high density, sustained and / or enhanced stability and / or functionality, sustained and / or enhanced ligand binding and / or microbiological stability).

[0098] In some embodiments, the particles in the compositions of this disclosure may comprise one or more microparticles, nanoparticles, microspheres, particles, fibers, beads, paramagnetic beads, magnetic beads, microbeads, nanobeads, amorphous materials, powders, or any combination thereof. Exemplary and non-limiting particle types that may be included in the compositions of this disclosure include silica beads, silica gel beads, glass beads with controllable porosity, magnetic beads, glass beads, borosilicate beads, paramagnetic beads, immunomagnetic beads, Sephadex / Sepharose beads, cellulose beads, polystyrene beads, mineral beads, crystalline particles, zircon particles, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof.

[0099] In some embodiments, the particles in the compositions of this disclosure may be functionalized. Any suitable functional group or portion may be attached, adhered, bound, or otherwise associated with the particles, including but not limited to carboxyl, amino, hydroxyl, silica, streptavidin, enzyme, amine, thiol, glycol, polymer, antibody or antibody fragment, nucleic acid, oligonucleotide, peptide, polypeptide, or any combination thereof.

[0100] The particles suitable for the compositions of this disclosure can have a variety of sizes. For example, the particles in the compositions of this disclosure can have sizes in the nanometer range, such as cross-sectional diameters, for example between about 1 nm and about 1000 nm, between about 10 nm and about 900 nm, between about 20 nm and about 800 nm, between about 30 nm and about 700 nm, between about 40 nm and about 600 nm, between about 50 nm and about 500 nm, between about 60 nm and about 400 nm, between about 70 nm and about 300 nm, between about 80 nm and about 200 nm, or between about 90 nm and about 100 nm, including any value in each of the said ranges. In some embodiments, the particles may have a size between about 100 nm and about 200 nm, such as a cross-sectional diameter, including any value within the range, such as about 105 nm, about 110 nm, about 115 nm, about 120 nm, about 125 nm, about 130 nm, about 135 nm, about 140 nm, about 145 nm, about 150 nm, about 155 nm, about 160 nm, about 165 nm, about 170 nm, about 175 nm, about 180 nm, about 185 nm, about 190 nm, about 195 nm, or about 200 nm. In some embodiments, the particles may have a size between about 200 nm and about 400 nm, such as a cross-sectional diameter, including any value within the range, such as any one of about 200 nm, about 210 nm, about 220 nm, about 230 nm, about 240 nm, about 250 nm, about 260 nm, about 270 nm, about 280 nm, about 290 nm, about 300 nm, about 310 nm, about 320 nm, about 330 nm, about 340 nm, about 350 nm, about 360 nm, about 370 nm, about 380 nm, about 390 nm, or about 400 nm. In some embodiments, the particles may have a size of about 300 nm, such as a cross-sectional diameter. In some embodiments, the particles may have a size between about 700 nm and about 900 nm, such as a cross-sectional diameter, including any value within the range, such as about 700 nm, about 710 nm, about 720 nm, about 730 nm, about 740 nm, about 750 nm, about 760 nm, about 770 nm, about 780 nm, about 790 nm, about 800 nm, about 810 nm, about 820 nm, about 830 nm, about 840 nm, about 850 nm, about 860 nm, about 870 nm, about 880 nm, about 890 nm, or about 900 nm.In some embodiments, the particles may have a size of about 800 nm, such as a cross-sectional diameter. In another example, the particles in the compositions of this disclosure may have a size in the micrometer range, such as a cross-sectional diameter, for example, between about 1 μm and about 1000 μm, between about 10 μm and about 900 μm, between about 20 μm and about 800 μm, between about 30 μm and about 700 μm, between about 40 μm and about 600 μm, between about 50 μm and about 500 μm, between about 60 μm and about 400 μm, between about 70 μm and about 300 μm, between about 80 μm and about 200 μm, or between about 90 μm and about 100 μm, including any value within each of the said ranges. In some embodiments, the particles in the compositions of this disclosure may have a size between about 1 μm and about 10 μm, such as a cross-sectional diameter, including any value within the range, such as any one of about 1 μm, about 2 μm, about 3 μm, about 4 μm, about 5 μm, about 6 μm, about 7 μm, about 8 μm, about 9 μm, or about 10 μm. In some embodiments, the particles in the compositions of this disclosure may have a size between about 10 μm and about 100 μm, such as a cross-sectional diameter, including any value within the range, such as any one of about 10 μm, about 20 μm, about 30 μm, about 40 μm, about 50 μm, about 60 μm, about 70 μm, about 80 μm, about 90 μm, or about 100 μm. In some embodiments, the particles in the compositions of this disclosure may have a size between about 100 μm and about 1000 μm, such as a cross-sectional diameter, including any value within the range, such as any one of about 100 μm, about 200 μm, about 300 μm, about 400 μm, about 500 μm, about 600 μm, about 700 μm, about 800 μm, about 900 μm, or about 1000 μm. In another example, the particles in the compositions of this disclosure may have a size in the millimeter range, such as a cross-sectional diameter, such as between about 1 mm and about 20 mm, between about 1 mm and about 15 mm, between about 1 mm and about 10 mm, or any one of about 1 mm and about 5 mm, including any value within each of the ranges. In some embodiments, the particles in the compositions disclosed herein may have a size between about 1 mm and about 10 mm, such as a cross-sectional diameter, including any value within the range, such as any one of about 1 mm, about 2 mm, about 3 mm, about 4 mm, about 5 mm, about 6 mm, about 7 mm, about 8 mm, about 9 mm, or about 10 mm.In some embodiments, the compositions disclosed herein may comprise a mixture of one or more particles of different sizes, for example, having different dimensions (e.g., different cross-sectional diameters).

[0101] In some embodiments, the particles in the compositions of this disclosure may be able to bind ligands or be configured to do so. Exemplary ligands include, but are not limited to, nucleic acids, cells, viral particles, peptides, lipids, carbohydrates, or small molecules.

[0102] In some embodiments, the particles in the compositions of this disclosure may be capable of or configured to bind nucleic acids, such as DNA, cDNA, and / or RNA. In this case, the particles may be silica or silica-coated particles, or particles associated with one or more oligonucleotides. The particles may be beads, microparticles, microspheres, microbeads, nanobeads, etc. The particles may also be magnetic or paramagnetic.

[0103] In other embodiments, the particles in the compositions of this disclosure may be capable of or configured to bind one or more proteins or peptides. In this case, the particles may be associated with protein A / G or modified with a carboxylate. The particles may be beads, microparticles, microspheres, microbeads, nanobeads, etc. The particles may also be magnetic or paramagnetic.

[0104] In some embodiments, the particles in the compositions of this disclosure can be used to aid in cell lysis (e.g., mechanical lysis) and / or homogenization of tissues or other sample types. In this case, the particles can be mineral beads, crystalline particles, zircon particles, zircon stones, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof.

[0105] The compositions disclosed herein may contain any suitable amount of particles. In some cases, the compositions disclosed herein may contain particles at concentrations of about 0.1% to about 99%, about 1% to about 90%, about 1% to about 80%, about 1% to about 70%, about 1% to about 60%, about 1% to about 50%, about 1% to about 40%, about 1% to about 30%, about 1% to about 20%, or about 1% to about 10% (w / v), including any value within each of the stated ranges. In some cases, the compositions disclosed herein may contain particles at a concentration of at least about 0.25%, at least about 0.5%, at least about 0.75%, at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 11%, at least about 12%, at least about 13%, at least about 14%, at least about 15%, at least about 16%, at least about 17%, at least about 18%, at least about 19%, at least about 20%, at least about 21%, at least about 22%, at least about 23%, at least about 24%, at least about 25%, at least about 26%, at least about 27%, at least about 28%, at least about 29%, or at least about 30% (w / v). In some embodiments, the compositions of this disclosure may comprise particles at a concentration between about 1% and about 20% w / v, including any value within that range, such as any one of about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20% w / v. In some embodiments, the compositions of this disclosure comprise particles at a concentration of about 10% w / v.

[0106] e. Other reagents

[0107] In some embodiments, the compositions of this disclosure may contain one or more other reagents, for example, depending on the intended use of the composition, storage conditions or duration, the specific type of particles in the composition, etc.

[0108] Exemplary reagents that may be included in the compositions disclosed herein include, but are not limited to, one or more of the following: buffers, such as phosphate buffers, citrate buffers, and buffers based on other organic acids; antioxidants, including ascorbic acid, methionine, glutathione, lipoic acid, uric acid, carotene, α-tocopherol, panthenol, tocopherol, propyl gallate, tert-butylhydroquinone, butylated hydroxyanisole, butylated hydroxytoluene, phenolic antioxidants such as stilbenes, flavonoids, and hydroxycinnamic acid, N,N'-di-2-butyl-1,4-phenylenediamine, N,N'-di-2-butyl-1,4-phenylenediamine, 2,6-di-tert-butyl-4-methylphenol, 2,4-dimethyl-6-tert-butylphenol, 2,4-dimethyl-6-tert-butylphenol, and 2,4-dimethyl-6-tert-butylphenol. Phenol, 2,4-dimethyl-6-tert-butylphenol, 2,6-di-tert-butyl-4-methylphenol, 2,6-di-tert-butylphenol, amine antioxidants, phytic acid, oxalic acid, tannins and combinations thereof; preservatives, such as octadecyl dimethyl benzyl ammonium chloride, hexamethyl ammonium chloride, benzalkonium chloride, benzyl ammonium chloride, phenol, butanol or benzyl alcohol, alkyl esters of p-hydroxybenzoate such as methylparaben or propylparaben, catechol, resorcinol, cyclohexanol, 3-pentanol or m-cresol; low molecular weight peptides (e.g., fewer than about 10 residues); proteins, such as serum albumin, gelatin or immunoglobulins; reducing agents, such as lithium aluminum hydride, Red-Al, hydrogen with or without a suitable catalyst (e.g., Lindra catalyst), sodium amalgam, sodium Lead alloys, zinc amalgams, diborane, sodium borohydride, ferrous compounds containing Fe2+ ions (e.g., ferrous sulfate), stannous compounds containing Sn2+ ions (e.g., stannous chloride), sulfur dioxide, sulfite compounds, dithionite, thiosulfate, iodides, hydrogen peroxide, hydrazine, diisobutylaluminum hydride, oxalic acid, formic acid, ascorbic acid, reducing sugars (e.g., erythrose), phosphites, hypophosphites, phosphorous acid, dithiothreitol (DTT), carbon monoxide (CO), cyanide, carbon, tris(2-carboxyethyl)phosphine hydrochloride (TCEP) or any combination thereof; hydrophilic polymers such as polyvinylpyrrolidone; amino acids such as glycine, glutamine, asparagine, histidine, arginine, or lysine; monosaccharides, disaccharides, and others. Carbohydrates, including glucose, mannose, or dextrin; chelating agents, such as disodium ethylenediaminetetraacetate, ethylene glycol-O,O'-bis(2-aminoethyl)-N,N,N',N'-tetraacetic acid, N-(2-hydroxyethyl)ethylenediamine-N,N',N'-triacetic acid trisodium salt, hypozoxytriacetic acid, 2,2'-bipyridine, dimercaprol, ethylenediaminetetraacetic acid, ethylenedioxydiethylenediazoxytriazoxytetraacetic acid, ethylene glycol-bis(2-aminoethyl)-N,N,N',N'-tetraacetic acid, ion carriers, hypozoxytriacetic acid, o-phenanthroline, salicylic acid, triethanolamine, and combinations thereof; sugars, such as sucrose, mannitol, trehalose, or sorbitol; salt-forming counterions, such as sodium; metal complexes (e.g., zinc-protein complexes);Surfactants, such as nonionic surfactants; or polymers, such as polyethylene glycol (PEG).

[0109] In some specific embodiments, the compositions disclosed herein may contain antioxidants, reducing agents, chelating agents, or any combination thereof.

[0110] In some embodiments, the compositions of this disclosure are microbiologically stable and may not require the use of antimicrobial agents or preservatives. Therefore, in some embodiments, the compositions of this disclosure do not contain antimicrobial agents and / or preservatives.

[0111] In some cases, for example, depending on the intended use of the compositions disclosed herein, it may be undesirable to include surfactants or detergents, or high amounts of surfactants or detergents, in the compositions disclosed herein due to, for example, foaming. Therefore, in some cases, the compositions disclosed herein are free of surfactants or detergents, while in other cases, the compositions disclosed herein contain less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 2.5%, or less than about 1% surfactants or detergents.

[0112] f. Exemplary Compositions

[0113] In some embodiments, the compositions of this disclosure comprise a plurality of particles, a mobile phase, and a viscosity enhancer. In some embodiments, the concentration of the mobile phase is about 70%, and the concentration of the viscosity enhancer is about 30% w / w. In some embodiments, the concentration of the mobile phase is about 80%, and the concentration of the viscosity enhancer is about 20% w / w. In some embodiments, the concentration of the mobile phase is about 90%, and the concentration of the viscosity enhancer is about 10% w / w. In some embodiments, the ratio of the mobile phase to the viscosity enhancer is about 2.33:1 w / w. In some embodiments, the ratio of the mobile phase to the viscosity enhancer is about 4:1 w / w. In some embodiments, the ratio of the mobile phase to the viscosity enhancer is about 9:1 w / w. In some embodiments, the mobile phase comprises a glycerol suspending agent. In some embodiments, the viscosity enhancer comprises PEG, such as PEG 4000, PEG 8000, PEG 10000, or PEG 20000. In some embodiments, the viscosity enhancer comprises PEG 8000. In some embodiments, the composition comprises: (a) a plurality of particles of glycerol at a concentration of about 70% and PEG 8000 at a concentration of about 30% w / w; (b) a plurality of particles of glycerol at a concentration of about 80% and PEG 8000 at a concentration of about 20% w / w; or (c) a plurality of particles of glycerol at a concentration of about 90% and PEG 8000 at a concentration of about 10% w / w. In some embodiments, the composition comprises a plurality of particles and: (a) glycerol and PEG 8000 in a ratio of about 2.33:1 w / w; (b) glycerol and PEG 8000 in a ratio of about 4:1 w / w; or (c) glycerol and PEG 8000 in a ratio of about 9:1 w / w.

[0114] In some embodiments, the compositions of this disclosure comprise a plurality of particles, a mobile phase, and a solubilizer. In some embodiments, the concentration of the mobile phase is about 70%, and the concentration of the solubilizer is about 30% w / w. In some embodiments, the concentration of the mobile phase is about 80%, and the concentration of the solubilizer is about 20% w / w. In some embodiments, the concentration of the mobile phase is about 90%, and the concentration of the solubilizer is about 10% w / w. In some embodiments, the ratio of mobile phase to solubilizer is about 2.33:1 w / w. In some embodiments, the ratio of mobile phase to solubilizer is about 4:1 w / w. In some embodiments, the ratio of mobile phase to solubilizer is 9:1 w / w. In some embodiments, the mobile phase comprises a glycerol suspending agent. In some embodiments, the solubilizer comprises a dissolving agent, such as urea, a water-soluble urea derivative, or a guanidine salt. In some embodiments, the solubilizer comprises urea. In some embodiments, the composition comprises: (a) a plurality of particles of glycerol at a concentration of about 70% and urea at a concentration of about 30% w / w; (b) a plurality of particles of glycerol at a concentration of about 80% and urea at a concentration of about 20% w / w; or (c) a plurality of particles of glycerol at a concentration of about 90% and urea at a concentration of about 10% w / w. In some embodiments, the composition comprises a plurality of particles and: (a) glycerol and urea in a ratio of about 2.33:1 w / w; (b) glycerol and urea in a ratio of about 4:1 w / w; or (c) glycerol and urea in a ratio of about 9:1 w / w.

[0115] In some embodiments, the compositions of this disclosure comprise a plurality of particles, a mobile phase, a viscosity enhancer, and a solubilizer. In some embodiments, the concentration of the mobile phase is about 70%, the concentration of the viscosity enhancer is about 25%, and the concentration of the solubilizer is about 5% w / w. In some embodiments, the concentration of the mobile phase is about 70%, the concentration of the viscosity enhancer is about 20%, and the concentration of the solubilizer is about 10% w / w. In some embodiments, the concentration of the mobile phase is about 70%, the concentration of the viscosity enhancer is about 15%, and the concentration of the solubilizer is about 15% w / w. In some embodiments, the concentration of the mobile phase is about 70%, the concentration of the viscosity enhancer is about 10%, and the concentration of the solubilizer is about 20% w / w. In some embodiments, the concentration of the mobile phase is about 70%, the concentration of the viscosity enhancer is about 5%, and the concentration of the solubilizer is about 25% w / w. In some embodiments, the concentration of the mobile phase is about 80%, the concentration of the viscosity enhancer is about 15%, and the concentration of the solubilizer is about 5% w / w. In some embodiments, the concentration of the mobile phase is about 80%, the concentration of the viscosity enhancer is about 10%, and the concentration of the solubilizer is about 10% w / w. In some embodiments, the concentration of the mobile phase is about 80%, the concentration of the viscosity enhancer is about 5%, and the concentration of the solubilizer is about 15% w / w. In some embodiments, the concentration of the mobile phase is about 78%, the concentration of the viscosity enhancer is about 7%, and the concentration of the solubilizer is about 15% w / w. In some embodiments, the concentration of the mobile phase is about 90%, the concentration of the viscosity enhancer is about 5%, and the concentration of the solubilizer is about 5% w / w. In some embodiments, the ratio of the mobile phase, viscosity enhancer, and solubilizer is about 14:5:1 w / w. In some embodiments, the ratio of the mobile phase, viscosity enhancer, and solubilizer is about 7:2:1 w / w. In some embodiments, the ratio of the mobile phase, viscosity enhancer, and solubilizer is about 4.7:1:1 w / w. In some embodiments, the ratio of the mobile phase, viscosity enhancer, and solubilizer is about 7:1:2 w / w. In some embodiments, the ratio of the mobile phase, viscosity enhancer, and solubilizer is about 14:1:5 w / w. In some embodiments, the ratio is about 16:3:1 w / w. In some embodiments, the ratio is about 8:1:1 w / w. In some embodiments, the ratio is about 16:1:3 w / w. In some embodiments, the ratio is about 15.6:1.4:3 w / w. In some embodiments, the ratio is about 18:1:1 w / w. In some embodiments, the mobile phase comprises a glycerol suspending agent. In some embodiments, the solubilizer comprises a liquid release agent, such as urea, a water-soluble urea derivative, or a guanidine salt. In some embodiments, the solubilizer comprises urea.In some embodiments, the viscosity enhancer comprises PEG, such as PEG 4000, PEG 8000, PEG 10000, or PEG 20000. In some embodiments, the viscosity enhancer comprises PEG 8000. In some embodiments, the viscosity enhancer comprises PEG 10000. In some embodiments, the suspending agent of the mobile phase comprises glycerol, the viscosity enhancer comprises PEG 8000, and the solubilizer comprises urea. In some embodiments, the suspending agent of the mobile phase comprises glycerol, the viscosity enhancer comprises PEG 10000, and the solubilizer comprises urea. In some specific embodiments, the composition comprises: (a) a plurality of particles, glycerol at a concentration of about 70%, PEG 8000 at a concentration of about 25%, and urea at a concentration of about 5% w / w; (b) a plurality of particles, glycerol at a concentration of about 70%, PEG 8000 at a concentration of about 20%, and urea at a concentration of about 10% w / w; (c) a plurality of particles, glycerol at a concentration of about 70%, PEG 8000 at a concentration of about 15%, and urea at a concentration of about 15% w / w; (d) a plurality of particles, glycerol at a concentration of about 70%, PEG 8000 at a concentration of about 10%, and urea at a concentration of about 20% w / w; (e) a plurality of particles, glycerol at a concentration of about 70%, PEG 8000 at a concentration of about 5%, and urea at a concentration of about 25% w / w; and (f) a plurality of particles, glycerol at a concentration of about 80%, and PEG 8000 at a concentration of about 15%. (g) PEG 8000 and urea at a concentration of about 5% w / w; (h) multiple particles of glycerol at a concentration of about 80%, PEG 8000 at a concentration of about 10%, and urea at a concentration of about 10% w / w; (i) multiple particles of glycerol at a concentration of about 90%, PEG 8000 at a concentration of about 5%, and urea at a concentration of about 5% w / w; or (j) multiple particles of glycerol at a concentration of about 78%, PEG 8000 at a concentration of about 7%, and urea at a concentration of about 15% w / w.In some specific embodiments, the composition comprises: (a) a plurality of particles, glycerol at a concentration of about 70%, PEG 10000 at a concentration of about 25%, and urea at a concentration of about 5% w / w; (b) a plurality of particles, glycerol at a concentration of about 70%, PEG 10000 at a concentration of about 20%, and urea at a concentration of about 10% w / w; (c) a plurality of particles, glycerol at a concentration of about 70%, PEG 10000 at a concentration of about 15%, and urea at a concentration of about 15% w / w; (d) a plurality of particles, glycerol at a concentration of about 70%, PEG 10000 at a concentration of about 10%, and urea at a concentration of about 20% w / w; (e) a plurality of particles, glycerol at a concentration of about 70%, PEG 10000 at a concentration of about 5%, and urea at a concentration of about 25% w / w; (f) Multiple particles containing approximately 80% glycerol, approximately 15% PEG 10000, and approximately 5% w / w urea; (g) multiple particles containing approximately 80% glycerol, approximately 10% PEG 10000, and approximately 10% w / w urea; (h) multiple particles containing approximately 80% glycerol, approximately 5% PEG 10000, and approximately 15% w / w urea; (i) multiple particles containing approximately 90% glycerol, approximately 5% PEG 10000, and approximately 5% w / w urea; or (j) multiple particles containing approximately 78% glycerol, approximately 7% PEG 10000, and approximately 15% w / w urea. In some specific embodiments, the composition comprises a plurality of particles and: (a) glycerol, PEG 8000, and urea in a ratio of about 14:5:1 w / w; (b) glycerol, PEG 8000, and urea in a ratio of about 7:2:1 w / w; (c) glycerol, PEG 8000, and urea in a ratio of about 4.7:1:1 w / w; (d) glycerol, PEG 8000, and urea in a ratio of about 7:1:2 w / w; (e) glycerol, PEG 8000, and urea in a ratio of about 14:1:5 w / w; (f) glycerol, PEG 8000, and urea in a ratio of about 16:3:1 w / w; (g) glycerol, PEG 8000, and urea in a ratio of about 8:1:1 w / w; (h) glycerol, PEG 8000, and urea in a ratio of about 16:1:3 w / w; (i) The ratio of glycerol, PEG 8000 and urea is approximately 18:1:1 w / w; or (j) the ratio of glycerol, PEG 8000 and urea is approximately 15.6:1.4:3 w / w.In some specific embodiments, the composition comprises a plurality of particles and: (a) glycerol, PEG 10000, and urea in a ratio of about 14:5:1 w / w; (b) glycerol, PEG 10000, and urea in a ratio of about 7:2:1 w / w; (c) glycerol, PEG 10000, and urea in a ratio of about 4.7:1:1 w / w; (d) glycerol, PEG 10000, and urea in a ratio of about 7:1:2 w / w; (e) glycerol, PEG 10000, and urea in a ratio of about 14:1:5 w / w; (f) glycerol, PEG 10000, and urea in a ratio of about 16:3:1 w / w; (g) glycerol, PEG 10000, and urea in a ratio of about 8:1:1 w / w; and (h) glycerol, PEG 10000, and urea in a ratio of about 16:1:3 w / w. 10000 and urea; (i) glycerol, PEG 10000 and urea in a ratio of about 18:1:1 w / w; or (j) glycerol, PEG10000 and urea in a ratio of about 15.6:1.4:3 w / w.

[0116] g. Physical properties

[0117] In some embodiments, the compositions of this disclosure are non-aqueous or substantially non-aqueous. For example, the water content of the compositions of this disclosure may be about 5% or less, about 4% or less, about 3% or less, about 2% or less, about 1% or less, about 0.5% or less, or about 0.25% or less. In some cases, the water content of the compositions of this disclosure is about 1% or less. The water content of the compositions of this disclosure can be assessed using any suitable method known in the art, such as Karl Fischer titration or gas chromatography. In some embodiments, the water content is assessed by Karl Fischer titration.

[0118] In some embodiments, the compositions of this disclosure may be liquid compositions and may have relatively high viscosity and / or density. In some cases, the compositions of this disclosure may be pastes, creams, or gels.

[0119] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 7000 mPa·s, at least about 7100 mPa·s, at least about 7200 mPa·s, at least about 7300 mPa·s, at least about 7400 mPa·s, at least about 7500 mPa·s, at least about 7600 mPa·s, at least about 7700 mPa·s, at least about 7800 mPa·s, at least about 7900 mPa·s, or at least about 8000 mPa·s when measured at a temperature of about 15°C; or between about 7000 mPa·s and about 8000 mPa·s, between about 7250 mPa·s and about 8000 mPa·s, between about 7500 mPa·s and about 8000 mPa·s, or between about 7750 mPa·s and about 8000 mPa·s when measured at a temperature of about 15°C. The values ​​are between mPa·s, including any value within each of the ranges.

[0120] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 5000 mPa·s, at least about 5100 mPa·s, at least about 5200 mPa·s, at least about 5300 mPa·s, at least about 5400 mPa·s, at least about 5500 mPa·s, at least about 5600 mPa·s, at least about 5700 mPa·s, at least about 5800 mPa·s, at least about 5900 mPa·s, or at least about 6000 mPa·s when measured at a temperature of about 20°C; or between about 5000 mPa·s and about 6000 mPa·s, between about 5250 mPa·s and about 6000 mPa·s, between about 5500 mPa·s and about 6000 mPa·s, or between about 5500 mPa·s and about 5750 mPa·s when measured at a temperature of about 20°C. The values ​​are between mPa·s, including any value within each of the ranges.

[0121] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 5500 mPa·s, at least about 5600 mPa·s, at least about 5700 mPa·s, at least about 5800 mPa·s, at least about 5900 mPa·s, at least about 6000 mPa·s, at least about 6100 mPa·s, at least about 6200 mPa·s, at least about 6300 mPa·s, at least about 6400 mPa·s, at least about 6500 mPa·s, at least about 6600 mPa·s, at least about 6700 mPa·s, at least about 6800 mPa·s, at least about 6900 mPa·s, or at least about 7000 mPa·s when measured at a temperature of about 25°C; or between about 5500 mPa·s and about 7000 mPa·s when measured at a temperature of about 25°C. Between mPa·s and about 6750 mPa·s, or between about 6000 mPa·s and about 6500 mPa·s, including any value within each of the ranges.

[0122] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 4200 mPa·s, at least about 4300 mPa·s, at least about 4400 mPa·s, at least about 4500 mPa·s, at least about 4600 mPa·s, at least about 4700 mPa·s, at least about 4800 mPa·s, at least about 4900 mPa·s, at least about 5000 mPa·s, at least about 5100 mPa·s, at least about 5200 mPa·s, at least about 5300 mPa·s, at least about 5400 mPa·s, or at least about 5500 mPa·s when measured at a temperature of about 30°C; or between about 4250 mPa·s and about 5500 mPa·s, between about 4500 mPa·s and about 5500 mPa·s, or at about 4750 mPa·s when measured at a temperature of about 30°C. Between mPa·s and about 5250 mPa·s, or between about 4750 mPa·s and about 5000 mPa·s, including any value within each of the ranges.

[0123] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 2000 mPa·s, at least about 2100 mPa·s, at least about 2200 mPa·s, at least about 2300 mPa·s, at least about 2400 mPa·s, at least about 2500 mPa·s, at least about 2600 mPa·s, at least about 2700 mPa·s, at least about 2800 mPa·s, at least about 2900 mPa·s, or at least about 3000 mPa·s when measured at about 35°C; or between about 2000 mPa·s and about 3000 mPa·s, between about 2250 mPa·s and about 2750 mPa·s, or between about 2250 mPa·s and about 2500 mPa·s when measured at about 35°C, including any value within each of the said ranges.

[0124] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 750 mPa·s, at least about 850 mPa·s, at least about 950 mPa·s, at least about 1050 mPa·s, at least about 1150 mPa·s, at least about 1250 mPa·s, at least about 1350 mPa·s, at least about 1450 mPa·s, at least about 1550 mPa·s, at least about 1650 mPa·s, or at least about 1750 mPa·s when measured at a temperature of about 40°C; or between about 750 mPa·s and about 1750 mPa·s, between about 1000 mPa·s and about 1750 mPa·s, or between about 1000 mPa·s and about 1500 mPa·s when measured at a temperature of about 40°C, including any value within each of the said ranges.

[0125] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 500 mPa·s, at least about 600 mPa·s, at least about 700 mPa·s, at least about 800 mPa·s, at least about 900 mPa·s, at least about 1000 mPa·s, at least about 1100 mPa·s, at least about 1200 mPa·s, at least about 1300 mPa·s, at least about 1400 mPa·s, or at least about 1500 mPa·s when measured at about 45°C; or between about 500 mPa·s and about 1500 mPa·s, between about 750 mPa·s and about 1250 mPa·s, or between about 1000 mPa·s and about 1250 mPa·s when measured at about 45°C, including any value within each of the said ranges.

[0126] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 250 mPa·s, at least about 350 mPa·s, at least about 450 mPa·s, at least about 550 mPa·s, at least about 650 mPa·s, at least about 750 mPa·s, at least about 850 mPa·s, at least about 950 mPa·s, at least about 1050 mPa·s, at least about 1150 mPa·s, at least about 1250 mPa·s, at least about 1350 mPa·s, at least about 1450 mPa·s, or at least about 1550 mPa·s when measured at about 50°C; or between about 250 mPa·s and about 1500 mPa·s, between about 500 mPa·s and about 1250 mPa·s, or between about 500 mPa·s and about 1000 mPa·s when measured at about 50°C. The values ​​are between mPa·s, including any value within each of the ranges.

[0127] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 500 mPa·s, at least about 600 mPa·s, at least about 700 mPa·s, at least about 800 mPa·s, at least about 900 mPa·s, at least about 1000 mPa·s, at least about 1100 mPa·s, at least about 1200 mPa·s, at least about 1300 mPa·s, at least about 1400 mPa·s, or at least about 1500 mPa·s when measured at about 55°C; or between about 500 mPa·s and about 1500 mPa·s, between about 750 mPa·s and about 1250 mPa·s, or between about 1000 mPa·s and about 1250 mPa·s when measured at about 55°C, including any value within each of the said ranges.

[0128] In some embodiments, the compositions of this disclosure have any of the following viscosities: at least about 100 mPa·s, at least about 150 mPa·s, at least about 200 mPa·s, at least about 250 mPa·s, at least about 300 mPa·s, at least about 350 mPa·s, at least about 400 mPa·s, at least about 450 mPa·s, at least about 500 mPa·s, at least about 550 mPa·s, or at least about 600 mPa·s when measured at a temperature of about 60°C; or between about 100 mPa·s and about 600 mPa·s, between about 200 mPa·s and about 500 mPa·s, or between about 200 mPa·s and about 400 mPa·s when measured at a temperature of about 60°C, including any value within each of the said ranges.

[0129] Viscosity can be evaluated using any suitable technique known in the art, such as a capillary viscometer, viscosity cup, Zain cup, falling ball viscometer, vibrational viscometer, rotational viscometer, or consistency meter. In some embodiments, a rotational viscometer is used to evaluate viscosity. In some cases, viscosity can be evaluated at a spindle speed of about 10 revolutions per minute (RPM). Viscosity can also be evaluated based on the adhesion of the composition to a surface, such as a plastic (e.g., polypropylene, polyethylene, polypropylene copolymer, polymethylpentene, polyvinyl chloride, polyethylene terephthalate G copolymer, polycarbonate, polysulfone, polystyrene, or Teflon) or glass surface. In some cases, viscosity is evaluated based on the adhesion of the composition to a polypropylene surface.

[0130] In some embodiments, the density of the compositions of this disclosure is at least about 1 g / mL, for example, any one of about 1 g / mL, about 1.2 g / mL, about 1.3 g / mL, about 1.4 g / mL, about 1.5 g / mL, about 1.6 g / mL, about 1.7 g / mL, about 1.8 g / mL, about 1.9 g / mL, about 2 g / mL, or higher. In some embodiments, the density of the composition is between about 0.5 g / mL and about 2 g / mL, between about 1 g / mL and about 2 g / mL, between about 1 g / mL and about 1.5 g / mL, or between about 1.1 g / mL and about 1.5 g / mL, including any value within each of the stated ranges. In some cases, the density of the composition is about 1.3 g / mL. The density of the compositions of this disclosure can be assessed using any suitable method known in the art, such as using an analytical balance, hydrometer, specific gravity bottle, or measuring bottle. In some embodiments, an analytical balance is used to assess the density.

[0131] In some embodiments, the compositions of this disclosure may have a pH between about 5 and about 10, between about 6 and about 9, or between about 7 and about 8, including any value within each of these ranges. In some embodiments, the compositions of this disclosure have a pH between about 7 and about 8, such as any one of about 7, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, or about 8. The pH of the composition can be assessed using any suitable method known in the art, such as colorimetry (e.g., using pH indicator paper or solution) or using a pH meter.

[0132] In some embodiments, the compositions of this disclosure exhibit at least some degree of adhesion to plastic surfaces (e.g., polypropylene, polyethylene, polypropylene copolymers, polymethylpentene, polyvinyl chloride, polyethylene terephthalate G copolymer, polycarbonate, polysulfone, polystyrene, or Teflon) and / or glass surfaces. In some embodiments, the compositions of this disclosure exhibit at least some degree of adhesion to polypropylene surfaces.

[0133] h. Stability and functionality

[0134] In some embodiments, the compositions of this disclosure can support and / or enhance the stability of particles in the composition. The stability of particles in the compositions of this disclosure can be assessed based on particle integrity (e.g., the degree of particle degradation or breakage), the degree of particle aggregation, and / or the retention of ligand-binding capacity.

[0135] In some cases, the particles in the compositions disclosed herein are stable for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, at least about The stability period is 24 months, at least about 25 months, at least about 26 months, at least about 27 months, at least about 28 months, at least about 29 months, at least about 30 months, at least about 31 months, at least about 32 months, at least about 33 months, at least about 34 months, at least about 35 months, at least about 36 months, at least about 37 months, at least about 38 months, at least about 39 months, at least about 40 months, at least about 41 months, at least about 42 months, at least about 43 months, at least about 44 months, at least about 45 months, at least about 46 months, at least about 47 months, or at least about 48 months. In some embodiments, the compositions of this disclosure are stable for at least about 1 month. In some embodiments, the compositions of this disclosure are stable for at least about 3 months. In some embodiments, the compositions of this disclosure are stable for at least about 4.5 months. In some embodiments, the compositions of this disclosure are stable for at least about 6 months. In some embodiments, the compositions of this disclosure are stable for at least about 9 months. In some embodiments, the compositions of this disclosure are stable for at least about 12 months. In some embodiments, the compositions of this disclosure are stable for at least about 15 months. In some embodiments, the compositions of this disclosure are stable for at least about 18 months. In some embodiments, the compositions of this disclosure are stable for at least about 21 months. In some embodiments, the compositions of this disclosure are stable for at least about 24 months. In some embodiments, the compositions of this disclosure are stable for at least about 36 months.

[0136] In some embodiments, for example, compared to a baseline or to corresponding particles in an aqueous solution, less than about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 5%, or about 1% of the particles in the compositions of this disclosure are degraded and / or broken down. In some embodiments, compared to the baseline or corresponding particles in an aqueous solution, after storage for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, at least about 24 months, at least about 25 months, at least about 26 months, at least about 27 months, at least about 28 months, at least about 29 months, at least about 30 months, to After approximately 31 months, at least approximately 32 months, at least approximately 33 months, at least approximately 34 months, at least approximately 35 months, at least approximately 36 months, at least approximately 37 months, at least approximately 38 months, at least approximately 39 months, at least approximately 40 months, at least approximately 41 months, at least approximately 42 months, at least approximately 43 months, at least approximately 44 months, at least approximately 45 months, at least approximately 46 months, at least approximately 47 months, or at least approximately 48 months, less than approximately 90%, approximately 85%, approximately 80%, approximately 75%, approximately 70%, approximately 65%, approximately 60%, approximately 55%, approximately 50%, approximately 45%, approximately 40%, approximately 35%, approximately 30%, approximately 25%, approximately 20%, approximately 15%, approximately 10%, approximately 5%, or approximately 1% of the particles in the disclosed compositions are degraded and / or broken.

[0137] In some embodiments, for example, compared to corresponding particles in an aqueous solution, the compositions of this disclosure can reduce the degradation and / or fragmentation of particles in the composition by at least about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%. In some implementations, the storage period is at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, at least about 24 months, or at least about 25 months. The reduction in particle degradation and / or breakage shall be assessed after at least approximately 26 months, at least approximately 27 months, at least approximately 28 months, at least approximately 29 months, at least approximately 30 months, at least approximately 31 months, at least approximately 32 months, at least approximately 33 months, at least approximately 34 months, at least approximately 35 months, at least approximately 36 months, at least approximately 37 months, at least approximately 38 months, at least approximately 39 months, at least approximately 40 months, at least approximately 41 months, at least approximately 42 months, at least approximately 43 months, at least approximately 44 months, at least approximately 45 months, at least approximately 46 months, at least approximately 47 months, or at least approximately 48 months.

[0138] In some embodiments, for example, compared to a baseline or to corresponding particles in an aqueous solution, less than about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 5%, or about 1% of the particles in the compositions of this disclosure are aggregated. In some embodiments, compared to the baseline or corresponding particles in an aqueous solution, after storage for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, at least about 24 months, at least about 25 months, at least about 26 months, at least about 27 months, at least about 28 months, at least about 29 months, at least about 30 months, the particle size distribution is as follows: After at least 31 months, at least 32 months, at least 33 months, at least 34 months, at least 35 months, at least 36 months, at least 37 months, at least 38 months, at least 39 months, at least 40 months, at least 41 months, at least 42 months, at least 43 months, at least 44 months, at least 45 months, at least 46 months, at least 47 months, or at least 48 months, less than about 90%, about 85%, about 80%, about 75%, about 70%, about 65%, about 60%, about 55%, about 50%, about 45%, about 40%, about 35%, about 30%, about 25%, about 20%, about 15%, about 10%, about 5%, or about 1% of the particles in the compositions disclosed herein aggregate.

[0139] In some embodiments, for example, compared to particles in an aqueous solution, the compositions of this disclosure can reduce particle aggregation in the composition by at least about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%. In some implementations, the storage period is at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, at least about 24 months, at least about 25 months. The reduction in particle aggregation was assessed after at least 26 months, at least 27 months, at least 28 months, at least 29 months, at least 30 months, at least 31 months, at least 32 months, at least 33 months, at least 34 months, at least 35 months, at least 36 months, at least 37 months, at least 38 months, at least 39 months, at least 40 months, at least 41 months, at least 42 months, at least 43 months, at least 44 months, at least 45 months, at least 46 months, at least 47 months, or at least 48 months.

[0140] In some embodiments, the particles in the compositions of this disclosure retain at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99%, or 100% ligand binding capacity compared to a baseline or corresponding particles in an aqueous solution. In some embodiments, compared to a baseline or corresponding particles in an aqueous solution, the particles are measured at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, at least about 24 months, at least about 25 months, at least about 26 months, at least about 27 months, at least about 28 months, at least about 29 months, at least about 30 months, or at least about 3 months. The ligand binding capacity is maintained at least approximately 25%, at least approximately 30%, at least approximately 35%, at least approximately 40%, at least approximately 45%, at least approximately 55%, at least approximately 60%, at least approximately 65%, at least approximately 70%, at least approximately 75%, at least approximately 80%, at least approximately 85%, at least approximately 90%, at least approximately 95%, at least approximately 95%, at least approximately 99%, or 100% for at least 1 month, at least approximately 32 months, at least approximately 33 months, at least approximately 34 months, at least approximately 35 months, at least approximately 36 months, at least approximately 37 months, at least approximately 48 months, at least approximately 42 months, at least approximately 43 months, at least approximately 44 months, at least approximately 45 months, at least approximately 46 months, at least approximately 47 months, or at least approximately 48 months.

[0141] In some embodiments, for example, compared to particles in an aqueous solution, the compositions of this disclosure enhance ligand binding of particles in the composition by at least about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%. In some embodiments, for example, compared to particles in an aqueous solution, the compositions of this disclosure enhance ligand binding of particles in the composition by at least about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20%. In some implementations, the storage period is at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, at least about 24 months, or at least about 25 months. The enhancement of the particle ligand binding was evaluated after at least approximately 26 months, at least approximately 27 months, at least approximately 28 months, at least approximately 29 months, at least approximately 30 months, at least approximately 31 months, at least approximately 32 months, at least approximately 33 months, at least approximately 34 months, at least approximately 35 months, at least approximately 36 months, at least approximately 37 months, at least approximately 38 months, at least approximately 39 months, at least approximately 40 months, at least approximately 41 months, at least approximately 42 months, at least approximately 43 months, at least approximately 44 months, at least approximately 45 months, at least approximately 46 months, at least approximately 47 months, or at least approximately 48 months.

[0142] In some embodiments, the plurality of particles in the compositions of this disclosure comprise one or more particles configured to or capable of binding nucleic acid ligands (e.g., DNA, cDNA, and / or RNA). In this case, the stability of the particles in the composition can be assessed based on the nucleic acid binding capacity of the particles in the composition. In some embodiments, such nucleic acid binding particles are silica particles, such as magnetic or paramagnetic silica particles. In some embodiments, the particles in the compositions of this disclosure retain at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, at least about 99%, or 100% nucleic acid binding capacity compared to a baseline or to corresponding particles in an aqueous solution. In some implementations, compared to a baseline, the particles are measured over a period of at least approximately 1 month, at least approximately 2 months, at least approximately 3 months, at least approximately 4 months, at least approximately 5 months, at least approximately 6 months, at least approximately 7 months, at least approximately 8 months, at least approximately 9 months, at least approximately 10 months, at least approximately 11 months, at least approximately 12 months, at least approximately 13 months, at least approximately 14 months, at least approximately 15 months, at least approximately 16 months, at least approximately 17 months, at least approximately 18 months, at least approximately 19 months, at least approximately 20 months, at least approximately 21 months, at least approximately 22 months, at least approximately 23 months, at least approximately 24 months, at least approximately 25 months, at least approximately 26 months, at least approximately 27 months, at least approximately 28 months, at least approximately 29 months, at least approximately 30 months, at least approximately 31 months, or at least... Maintain at least approximately 25%, at least approximately 30%, at least approximately 35%, at least approximately 40%, at least approximately 44%, at least approximately 45%, at least approximately 50%, at least approximately 55%, at least approximately 60%, at least approximately 65%, at least approximately 70%, at least approximately 75%, at least approximately 80%, at least approximately 85%, at least approximately 90%, at least approximately 95%, at least approximately 95%, at least approximately 99%, or 100% nucleic acid binding capacity for approximately 32 months, at least approximately 33 months, at least approximately 34 months, at least approximately 35 months, at least approximately 36 months, at least approximately 37 months, at least approximately 40 months, at least approximately 41 months, at least approximately 42 months, at least approximately 43 months, at least approximately 44 months, at least approximately 45 months, at least approximately 46 months, at least approximately 47 months, or at least approximately 48 months. In some embodiments, for example, compared to particles in an aqueous solution, the compositions of this disclosure can enhance nucleic acid binding of particles in the composition by at least about 1%, about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, or about 100%.In some embodiments, for example, compared to particles in an aqueous solution, the compositions of this disclosure enhance nucleic acid binding of particles in the composition by at least about 1%, about 2%, about 3%, about 4%, about 5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 11%, about 12%, about 13%, about 14%, about 15%, about 16%, about 17%, about 18%, about 19%, or about 20%. In some embodiments, the compositions are stored for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, at least about 24 months, or at least about 25 months. The enhancement of nucleic acid binding of the said particles was assessed after at least approximately 26 months, at least approximately 27 months, at least approximately 28 months, at least approximately 29 months, at least approximately 30 months, at least approximately 31 months, at least approximately 32 months, at least approximately 33 months, at least approximately 34 months, at least approximately 35 months, at least approximately 36 months, at least approximately 37 months, at least approximately 38 months, at least approximately 39 months, at least approximately 40 months, at least approximately 41 months, at least approximately 42 months, at least approximately 43 months, at least approximately 44 months, at least approximately 45 months, at least approximately 46 months, at least approximately 47 months, or at least approximately 48 months.

[0143] Particle stability (e.g., assessed based on particle integrity, degree of particle aggregation, and / or retention of ligand binding capacity) can be assessed under a variety of conditions, such as normal atmospheric conditions, hypoxic conditions, nitrogen atmosphere, and at a variety of temperatures, such as between about -80°C and about 100°C, between about -20°C and about 90°C, between about -10°C and about 80°C, between about 0°C and about 70°C, between about 2°C and about 60°C, between about 4°C and about 50°C, between about 5°C and about 40°C, between about 10°C and about 30°C, between about 15°C and about 30°C, or between about 20°C and about 30°C, including any value within each of these ranges. In some embodiments, particle stability can be assessed at approximately room temperature, such as at about 20°C, about 21°C, about 22°C, about 23°C, about 24°C, or about 25°C. In some embodiments, particle stability is assessed under normal atmospheric conditions. In some embodiments, particle stability is assessed under hypoxic conditions (e.g., relative to normal atmospheric conditions). In some embodiments, particle stability is assessed in nitrogen. In some embodiments, particle stability is assessed at a temperature of about 25°C, under normal atmospheric conditions, under low-oxygen conditions (e.g., relative to normal atmospheric conditions), or in nitrogen.

[0144] The compositions disclosed herein have the advantage of microbiological stability. In some cases, the compositions disclosed herein have microbiological stability for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, at least about 15 months, at least about 16 months, at least about 17 months, at least about 18 months, at least about 19 months, at least about 20 months, at least about 21 months, at least about 22 months, at least about 23 months, and so on. At least 24 months, at least 25 months, at least 26 months, at least 27 months, at least 28 months, at least 29 months, at least 30 months, at least 31 months, at least 32 months, at least 33 months, at least 34 months, at least 35 months, at least 36 months, at least 37 months, at least 38 months, at least 39 months, at least 40 months, at least 41 months, at least 42 months, at least 43 months, at least 44 months, at least 45 months, at least 46 months, at least 47 months, or at least 48 months. Microbiological stability (e.g., assessed based on resistance to microbial growth) can be assessed under a variety of conditions, such as normal atmospheric conditions, hypoxic conditions, nitrogen atmosphere, and at a variety of temperatures, such as between about -80°C and about 100°C, between about -20°C and about 90°C, between about -10°C and about 80°C, between about 0°C and about 70°C, between about 2°C and about 60°C, between about 4°C and about 50°C, between about 5°C and about 40°C, between about 10°C and about 30°C, between about 15°C and about 30°C, or between about 20°C and about 30°C, including any value within each of these ranges. In some embodiments, microbiological stability can be assessed at approximately room temperature, such as at about 20°C, about 21°C, about 22°C, about 23°C, about 24°C, or about 25°C. In some embodiments, microbiological stability can be assessed under normal atmospheric conditions. In some embodiments, microbiological stability can be assessed under hypoxic conditions (e.g., relative to normal atmospheric conditions). In some embodiments, microbiological stability can be assessed in nitrogen. In some embodiments, microbiological stability is assessed at a temperature of about 25°C, under normal atmospheric conditions, under hypoxic conditions (e.g., relative to normal atmospheric conditions), or in nitrogen.

[0145] III. Method for preparing the composition

[0146] This document also provides methods for preparing compositions comprising multiple particles. The methods described herein can be used to prepare any composition disclosed herein.

[0147] In some embodiments, a composition comprising a plurality of particles is prepared by suspending the particles in a formulation comprising one, two, or all of the following: a mobile phase (e.g., any mobile phase provided herein), a viscosity enhancer (e.g., any viscosity enhancer provided herein), and a solubilizer (e.g., any solubilizer provided herein). In some embodiments, the particles are suspended in a formulation comprising: a mobile phase (e.g., any mobile phase provided herein) and a solubilizer (e.g., any solubilizer provided herein). In some embodiments, the particles are suspended in a formulation comprising: a mobile phase (e.g., any mobile phase provided herein) and a viscosity enhancer (e.g., any viscosity enhancer provided herein). In some embodiments, the particles are suspended in a formulation comprising: a viscosity enhancer (e.g., any viscosity enhancer provided herein) and a solubilizer (e.g., any solubilizer provided herein). In some embodiments, the particles are suspended in a formulation comprising: a mobile phase (e.g., any mobile phase provided herein), a viscosity enhancer (e.g., any viscosity enhancer provided herein), and a solubilizer (e.g., any solubilizer provided herein). Particles can be suspended in a formulation by mixing, stirring, grinding, milling, heating, ultrasonic mixing, and / or any other suitable method known in the art. In some embodiments, ultrasonic mixing is used to suspend particles in the formulation.

[0148] In some embodiments, the particles to be suspended in the formulation are or have been previously dehydrated or lyophilized. In other embodiments, a method of preparing a composition comprising a plurality of particles includes the step of dehydrating or lyophilizing the particles before suspending them in the formulation. For example, such dehydration or lyophilization can be performed when the particles are provided in the form of an aqueous suspension. Any suitable method known in the art can be used to dehydrate or lyophilize the particles. In some embodiments, the particles are lyophilized by manifold drying, batch drying, or bulk drying. In other embodiments, the particles are dehydrated by a stepwise phase change (e.g., from an aqueous phase to an organic phase) or spray drying.

[0149] In some embodiments, dehydration of the particles includes suspending the particles in a first organic solvent. In some embodiments, the method includes washing with an organic solvent once or multiple times (e.g., one, two, three, four, or more washes). In some embodiments, the method includes: (i) separating the particles stored in the aqueous solution from the aqueous solution, and (ii) suspending the separated particles in the first organic solvent. In some embodiments, one or more additional first organic solvent washes are performed, for example by (i) separating the particles from the first organic solvent, and (ii) resuspending the separated particles in another volume of the first organic solvent. In some embodiments, at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or more washes with the first organic solvent are performed. In some cases, two organic solvent washes are performed.

[0150] In other embodiments, dehydration of the particles includes a stepwise phase transition from an aqueous phase to an organic phase by washing the particles with a solution having an increasing concentration of organic solvent. In some embodiments, the dehydration includes suspending the particles in a first organic solvent with an increasing solvent concentration. For example, in some embodiments, the particles are dehydrated by: (i) separating the particles stored in an aqueous solution from the aqueous solution, and (ii) suspending the separated particles in a series of volumes of a mixture containing the first organic solvent, wherein each volume in the series has an increasing amount of organic solvent, for example, ranging from about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, or about 80% to about 100%. For example, the first volume in the series may contain an organic solvent concentration between about 20% and about 80%, including any value within the range, and the last volume in the series may contain about 99% or 100% of the organic solvent concentration. In another example, the first volume in the series contains approximately 50% organic solvent concentration, and the last volume in the series contains approximately 99% or 100% organic solvent concentration. In some embodiments, the series comprises approximately 2 to approximately 15 volumes, approximately 2 to approximately 10 volumes, or approximately 5 to approximately 7 volumes, including any value within each of the stated ranges. For example, in the case where the series comprises 5 volumes, the first volume may contain approximately 52% organic solvent concentration, the second volume may contain approximately 64% organic solvent concentration, the third volume may contain approximately 76% organic solvent concentration, the fourth volume may contain approximately 88% organic solvent concentration, and the fifth volume may contain approximately 99% or 100% organic solvent concentration. When the series comprises six volumes, the first volume may contain approximately 50% organic solvent concentration, the second volume approximately 60%, the third volume approximately 70%, the fourth volume approximately 80%, the fifth volume approximately 90%, and the sixth volume approximately 99% or 100% organic solvent concentration. When the series comprises seven volumes, the first volume may contain approximately 50% organic solvent concentration, the second volume approximately 55%, the third volume approximately 60%, the fourth volume approximately 65%, the fifth volume approximately 70%, the sixth volume approximately 85%, and the seventh volume approximately 99% or 100% organic solvent concentration.

[0151] In some embodiments, the first organic solvent is an organic solvent that is miscible with water and / or soluble in water.

[0152] In some cases, the first organic solvent comprises an aprotic solvent, such as a polar aprotic solvent. In some embodiments, the polar aprotic solvent is a dipolar aprotic solvent. Any suitable aprotic solvent known in the art can be used. Exemplary aprotic solvents that can be used include, but are not limited to, dimethyl sulfoxide (DMSO), dimethyl sulfone, tetrahydrofuran (THF), diphenyl sulfone (DPS), diethylene sulfoxide, diethyl sulfone, diisopropyl sulfone, propylene carbonate, acetonitrile, sulfolane, tetrahydrothiophene-1-monooxide, N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), and any combination thereof. In some embodiments, the aprotic solvent comprises sulfolane. In some embodiments, the aprotic solvent comprises DMSO.

[0153] In some embodiments, the first organic solvent is a water-miscible p- or e-type glycol ether, such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, ethylene glycol monoisopropyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monobenzyl ether, propylene glycol methyl ether, diethylene glycol ethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, diethylene glycol mono-n-butyl ether, dipropylene glycol methyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, ethylene glycol methyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, propylene glycol methyl ether acetate, or any combination thereof. In some embodiments, the first organic solvent is dipropylene glycol methyl ether and / or diethylene glycol ethyl ether.

[0154] In some embodiments, the first organic solvent is an alcohol, such as a monohydric alcohol, polyhydric alcohol, unsaturated fatty alcohol, or alicyclic alcohol. In some embodiments, the alcohol is tert-amyl alcohol, benzyl alcohol, 1,4-butanediol, 1,2,4-butanetriol, butanol, 1-butanol, 2-butanol, tert-butanol, denatured alcohol, di(propylene glycol) methyl ether, diethylene glycol, ethanol, ethylene glycol, 2-ethylhexanol, furfuryl alcohol, glycerol, isobutanol, isopropyl alcohol (isopropanol), methanol, 2-(2-methoxyethoxy)ethanol, 2-methyl-1-butanol, 2-methyl-1-pentanol, 3-methyl-2-butanol, neopentanol, 2-pentanol, 1,3-propanediol, propylene-1-ol, propylene glycol, propylene glycol methyl ether, or any combination thereof. In some embodiments, the alcohol is ethanol and / or isopropyl alcohol (isopropanol). When the first organic solvent is an alcohol, dehydration of the particles may include suspending the particles in an alcohol with a gradually increasing alcohol concentration. For example, in some embodiments, the particles are dehydrated by: (i) separating the particles stored in an aqueous solution from the aqueous solution, and (ii) suspending the separated particles in a series of volumes containing the alcohol, wherein each volume in the series has an incremental amount of alcohol, for example, ranging from about 20% to about 100%, about 30% to about 100%, about 40% to about 100%, about 50% to about 100%, about 60% to about 100%, about 70% to about 100%, or about 80% to about 100%, including any value within each of the said ranges. For example, the first volume in the series contains an alcohol concentration between about 20% and about 80%, including any value within the said range, and the last volume in the series may contain about 99% or 100% alcohol concentration. In another example, the first volume in the series contains about 50% alcohol concentration, and the last volume in the series contains about 99% or 100% alcohol concentration. In some embodiments, the series of volumes includes about 2 to about 15 volumes, about 2 to about 10 volumes, or about 5 to about 7 volumes, including any value within each of the said ranges. For example, if the series of volumes includes 5 volumes, the first volume may contain about 52% alcohol concentration, the second volume may contain about 64% alcohol concentration, the third volume may contain about 76% alcohol concentration, the fourth volume may contain about 88% alcohol concentration, and the fifth volume may contain about 99% or 100% alcohol concentration. If the series of volumes includes 6 volumes, the first volume may contain about 50% alcohol concentration, the second volume may contain about 60% alcohol concentration, the third volume may contain about 70% alcohol concentration, the fourth volume may contain about 80% alcohol concentration, the fifth volume may contain about 90% alcohol concentration, and the sixth volume may contain about 99% or 100% alcohol concentration.In the case of a series of seven volumes, the first volume may contain approximately 50% alcohol concentration, the second volume may contain approximately 55% alcohol concentration, the third volume may contain approximately 60% alcohol concentration, the fourth volume may contain approximately 65% ​​alcohol concentration, the fifth volume may contain approximately 70% alcohol concentration, the sixth volume may contain approximately 85% alcohol concentration, and the seventh volume may contain approximately 99% or 100% alcohol concentration.

[0155] In some embodiments, the first organic solvent is a mixture of two or more solvents, such as any solvent described herein and / or any suitable solvent known in the art. In some embodiments, the first organic solvent comprises a mixture of a polar aprotic solvent and an alcohol, such as a mixture of DMSO and ethanol, or a mixture of DMSO and isopropanol. In some embodiments, the first organic solvent comprises a mixture of two or more solvents of the same type, such as a mixture of two or more aprotic solvents, such as DMSO and THF. In some embodiments, the solvent ratio in the solvent mixture is about 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, or 1:3. In some embodiments, the solvent ratio in the solvent mixture is about 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20 or any other suitable ratio.

[0156] In some embodiments, dehydrated or lyophilized particles are directly suspended in a formulation comprising one or more of the following: a mobile phase (e.g., any mobile phase provided herein), a viscosity enhancer (e.g., any viscosity enhancer provided herein), and a solubilizer (e.g., any solubilizer provided herein). In other embodiments, the dehydrated or lyophilized particles are first suspended in a solution comprising a second organic solvent and / or a suspending agent before being suspended in the formulation. In this case, the method may include (i) separating a plurality of particles from a volume of a first organic solvent, and (ii) suspending the separated plurality of particles in a first volume of a solution comprising a second organic solvent and / or a suspending agent. In some embodiments, one or more additional washes with the solution are performed, for example by (i) separating a plurality of particles from the solution, and (ii) resuspending the separated plurality of particles in another volume of the solution. In some embodiments, at least one, at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least ten, or more washes with the solution are performed. In some cases, washing with the solution is performed once or twice. In some embodiments, the particles are then separated from the solution and subsequently suspended in a formulation comprising one or more of the following: a mobile phase (e.g., any mobile phase provided herein), a viscosity enhancer (e.g., any viscosity enhancer provided herein), and a solubilizer (e.g., any solubilizer provided herein). In some embodiments, the particles are suspended in a formulation comprising: a mobile phase (e.g., any mobile phase provided herein) and a solubilizer (e.g., any solubilizer provided herein). In some embodiments, the particles are suspended in a formulation comprising: a mobile phase (e.g., any mobile phase provided herein) and a viscosity enhancer (e.g., any viscosity enhancer provided herein). In some embodiments, the particles are suspended in a formulation comprising: a viscosity enhancer (e.g., any viscosity enhancer provided herein) and a solubilizer (e.g., any solubilizer provided herein). In some embodiments, the particles are suspended in a formulation comprising: a mobile phase (e.g., any mobile phase provided herein), a viscosity enhancer (e.g., any viscosity enhancer provided herein), and a solubilizer (e.g., any solubilizer provided herein). In some embodiments, the ratio of the second organic solvent to the suspending agent in the solution is about 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, or 1:3.In some embodiments, the ratio of the second organic solvent to the suspending agent in the solution is about 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or any other suitable ratio. In some embodiments, the ratio of the second organic solvent to the suspending agent in the solution is about 1:1.

[0157] Exemplary suspending agents that can be used in the solution include, but are not limited to, sugar alcohols, glycols, water-miscible polymers, aprotic solvents, and any combination thereof. In some embodiments, the suspending agent comprises a sugar alcohol. Any suitable sugar alcohol known in the art can be used. Exemplary sugar alcohols that can be used include, but are not limited to, glycerol, sorbitol, erythritol, threitol, arabinitol, xylitol, ribitol, mannitol, galactitol, fucitol, idoterol, inositol, heptaheptaol, isomaltitol, maltitol, lactitol, maltotriol, maltotetratitol, polyglycol, and any combination thereof. In some embodiments, the sugar alcohol comprises glycerol. In some embodiments, the suspending agent comprises a glycol. Any suitable glycol known in the art can be used. Exemplary glycols that can be used include, but are not limited to, diethylene glycol, ethylene glycol, hexanediol, propylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, glycol ethers, and any combination thereof. In some embodiments, the suspending agent in the compositions disclosed herein comprises propylene glycol. In some embodiments, the suspending agent comprises a water-miscible polymer. Any suitable water-miscible polymer known in the art can be used. Exemplary water-miscible polymers that can be used include, but are not limited to, acrylic polymers, ether polymers, epoxy polymers, polyethylene polymers, polyethylene glycol polymers, polystyrene polymers, polyvinyl chloride polymers, polytetrafluoroethylene polymers, polydimethylsiloxane polymers, polyester polymers, poly(N-vinylpyrrolidone) polymers, polystyrene copolymers, polyvinyl alcohol (PVA), polyurethane polymers, and any combination thereof. In some embodiments, the water-miscible polymer comprises a polyethylene glycol (PEG) polymer. In some embodiments, the average molecular weight of the water-miscible polymer is about 1000 g / mol or less, about 900 g / mol or less, about 800 g / mol or less, about 700 g / mol or less, about 600 g / mol or less, about 500 g / mol or less, about 400 g / mol or less, about 300 g / mol or less, about 200 g / mol or less, or about 100 g / mol or less. In some embodiments, the average molecular weight of the water-miscible polymer is about 300 g / mol or less, about 200 g / mol or less, or about 100 g / mol or less. In some embodiments, the average molecular weight of the water-miscible polymer is between about 100 g / mol and about 2000 g / mol, between about 100 g / mol and about 1000 g / mol, between about 200 g / mol and about 600 g / mol, between about 200 g / mol and about 400 g / mol, or between about 200 g / mol and about 300 g / mol.In some embodiments, the water-miscible polymer has an average molecular weight of about 100 g / mol, about 200 g / mol, about 300 g / mol, about 400 g / mol, about 500 g / mol, about 600 g / mol, about 700 g / mol, about 800 g / mol, about 900 g / mol, or about 1000 g / mol. In some embodiments, the water-miscible polymer has an average molecular weight of about 200 g / mol or about 300 g / mol. In some embodiments, the water-miscible polymer is a PEG polymer, such as PEG 200, PEG 300, PEG 400, PEG 600, or PEG 1000. In some embodiments, the water-miscible polymer is PEG 200 and / or PEG 300. In some embodiments, the suspending agent comprises an aprotic solvent. In some embodiments, the aprotic solvent is a polar aprotic solvent. In some embodiments, the aprotic solvent is a dipolar aprotic solvent. Any suitable aprotic solvent known in the art can be used. Exemplary aprotic solvents that can be used include, but are not limited to, dimethyl sulfoxide (DMSO), dimethyl sulfone, diphenyl sulfone (DPS), diethylene sulfoxide, diethyl sulfone, diisopropyl sulfone, sulfolane, tetrahydrothiophene-1-monoxide, THF, N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), and any combination thereof. In some embodiments, the aprotic solvent comprises sulfolane.

[0158] In some embodiments, the second organic solvent is an organic solvent miscible with and / or soluble in water. In some cases, the second organic solvent comprises an aprotic solvent, such as a polar aprotic solvent. In some embodiments, the polar aprotic solvent is a dipolar aprotic solvent. Any suitable aprotic solvent known in the art can be used. Exemplary aprotic solvents that can be used include, but are not limited to, dimethyl sulfoxide (DMSO), dimethyl sulfone, tetrahydrofuran (THF), acetonitrile, diphenyl sulfone (DPS), diethylene sulfoxide, diethyl sulfone, diisopropyl sulfone, propylene carbonate, sulfolane, tetrahydrothiophene-1-monooxide, N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), and any combination thereof. In some embodiments, the aprotic solvent comprises sulfolane. In some embodiments, the aprotic solvent comprises DMSO. In some embodiments, the second organic solvent is a water-miscible p- or E-type glycol ether, such as ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol monopropyl ether, ethylene glycol monoisopropyl ether, ethylene glycol monobutyl ether, ethylene glycol monophenyl ether, ethylene glycol monobenzyl ether, propylene glycol methyl ether, diethylene glycol monomethyl ether, diethylene glycol ethyl ether, diethylene glycol monoethyl ether, diethylene glycol mono-n-butyl ether, dipropylene glycol methyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, ethylene glycol dibutyl ether, ethylene glycol methyl ether acetate, ethylene glycol monoethyl ether acetate, ethylene glycol monobutyl ether acetate, propylene glycol methyl ether acetate, or any combination thereof. In some embodiments, the second organic solvent is dipropylene glycol methyl ether and / or diethylene glycol ethyl ether. In some embodiments, the second organic solvent is an alcohol, such as a monohydric alcohol, polyhydric alcohol, unsaturated fatty alcohol, or alicyclic alcohol. In some embodiments, the alcohol is tert-amyl alcohol, benzyl alcohol, 1,4-butanediol, 1,2,4-butanetriol, butanol, 1-butanol, 2-butanol, tert-butanol, denatured alcohol, di(propylene glycol) methyl ether, diethylene glycol, ethanol, ethylene glycol, 2-ethylhexanol, furfuryl alcohol, glycerol, isobutanol, isopropanol, methanol, 2-(2-methoxyethoxy)ethanol, 2-methyl-1-butanol, 2-methyl-1-pentanol, 3-methyl-2-butanol, neopentanol, 2-pentanol, 1,3-propanediol, propylene-1-ol, propylene glycol, propylene glycol methyl ether, or any combination thereof. In some embodiments, the alcohol is ethanol and / or isopropanol (isopropyl alcohol). In some embodiments, the second organic solvent is a mixture of two or more solvents, such as any solvent described herein and / or any suitable solvent known in the art. In some embodiments, the second organic solvent comprises a mixture of a polar aprotic solvent and an alcohol, such as a mixture of DMSO and ethanol, or a mixture of DMSO and isopropanol. In some embodiments, the second organic solvent comprises a mixture of two or more solvents of the same type, such as a mixture of two or more aprotic solvents, such as DMSO and THF.In some embodiments, the solvent ratio in the solvent mixture is about 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, or 1:3. In some embodiments, the solvent ratio in the solvent mixture is about 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12, 1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, 1:20, or any other suitable ratio. In some embodiments, the second organic solvent is the same as the first organic solvent. For example, both the first and second organic solvents can be DMSO. In other embodiments, the second organic solvent is different from the first organic solvent.

[0159] In some respects, this document also provides compositions comprising multiple particles produced by any of the methods for preparing compositions provided herein.

[0160] IV. Uses

[0161] Further aspects of this disclosure relate to the use of any of the compositions described herein, such as in methods of separating analytes from samples, methods of lysing cells, methods of grinding or homogenizing tissues or other sample types, and other uses that are obvious to those skilled in the art.

[0162] In one instance, the compositions of this disclosure can be used in a method for separating one or more analytes from a sample. In this case, the method may include providing a sample containing the analyte to be separated and mixing the sample or a portion thereof with the compositions of this disclosure, thereby binding the analyte to be separated from the sample to particles in the composition. In some embodiments, the method further includes separating the particles from the mixture of the sample or a portion thereof and the composition. For example, if the particles are magnetic or paramagnetic, a magnetic field may be used to separate the particles. Particles may also be separated by allowing them to settle or by using a centrifuge. In some cases, the method further includes transferring the separated particles to a different container (e.g., a new tube) or discarding the supernatant separated from the particles. In some cases, the method may include washing the separated particles in one or more steps (e.g., with a washing solution or buffer). In some embodiments, the method further includes eluting the bound analyte from the particles, for example, using an elution buffer, by heating, by changing the pH, by changing the salt concentration, or any other suitable elution method known in the art. In some cases, the method further includes recovering the eluted analyte, for example, by transferring the eluted analyte to a different container (e.g., a new tube). The analytes to be separated can be, for example, but not limited to, nucleic acids, cells, viral particles, peptides, lipids, carbohydrates, or small molecules.

[0163] The particles used in methods for separating analytes can be any suitable particles known in the art or described herein. In some embodiments, the particles can be beads, microparticles, microspheres, microbeads, nanobeads, etc. The particles can also be magnetic or paramagnetic. In some embodiments, the particles comprise one or more silica beads, silica gel beads, glass beads with controllable porosity, magnetic beads, glass beads, paramagnetic beads, immunomagnetic beads, Sephadex / Sepharose beads, cellulose beads, polystyrene beads, mineral beads, crystalline particles, zircon particles, zirconium particles, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof. In some cases, the particles may be functionalized. Any suitable functional group or portion may be attached, bonded, bound, or otherwise associated with the particles, including but not limited to carboxyl, amino, hydroxyl, silica, streptavidin, enzyme, amine, thiol, glycol, polymer, antibody or antibody fragment, nucleic acid, oligonucleotide, peptide, polypeptide, or any combination thereof. In some embodiments, the analyte is DNA, cDNA, and / or RNA. In this case, the particles may be able to or configured to bind nucleic acids, such as DNA, cDNA, and / or RNA. For example, the particles may be silica or silica-coated particles, or particles associated with one or more oligonucleotides.

[0164] In another instance, the compositions of this disclosure can be used to lyse one or more cells from a sample. In this case, the method may include providing a sample containing one or more cells and mixing the sample or a portion thereof with the compositions of this disclosure. In some embodiments, the method further includes stirring the mixture of the sample or a portion thereof with the compositions of this disclosure to lyse the one or more cells. Stirring may be performed manually, using a vortex apparatus, stirring (e.g., using a magnetic stir bar), using a bead mill, sonication, or other suitable methods. In some embodiments, the method further includes separating particles from the mixture of the sample or a portion thereof and the composition. For example, if the particles are magnetic or paramagnetic, a magnetic field may be used to separate the particles. Particles may also be separated by allowing them to settle or by using a centrifuge. In some cases, the method further includes transferring the supernatant separated from the particles to a separate container (e.g., a new tube) and / or discarding the separated beads. The cells to be lysed may be prokaryotic cells, eukaryotic cells, or both. Examples of cells that can be lysed according to the methods provided herein include, but are not limited to, one or more animal cells, plant cells, mammalian cells, bacterial cells, archaea cells, fungal cells, protozoan cells, algal cells, or any combination thereof. The particles used in the cell lysis method of this disclosure can be any type of particle known in the art or described herein as suitable for such use, such as, but not limited to, mineral beads, crystalline particles, zircon particles, zircon stones, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof. The particles can also be magnetic or paramagnetic.

[0165] In another instance, the compositions of this disclosure can be used to homogenize or grind tissue samples or other types of samples. In this case, the method may include providing a sample, such as a tissue sample, and mixing the sample or a portion thereof with the compositions of this disclosure. In some embodiments, the method further includes stirring the mixture of the sample or a portion thereof with the compositions of this disclosure to grind and / or homogenize the sample. Stirring can be performed manually, using a vortex apparatus, stirring (e.g., using a magnetic stir bar), using a bead mill, ultrasonication, or other suitable methods. In some embodiments, the method further includes separating particles from the mixture of the sample or a portion thereof and the composition. For example, if the particles are magnetic or paramagnetic, a magnetic field can be used to separate the particles. Particles can also be separated by allowing them to settle or by using a centrifuge. In some cases, the method further includes transferring the supernatant separated from the particles to a separate container (e.g., a new tube) and / or discarding the separated beads. The particles used in the homogenization or grinding methods of this disclosure can be any type of particle known in the art or described herein as suitable for such applications, such as, but not limited to, mineral beads, crystalline particles, zircon particles, zircon stone particles, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof. The particles can also be magnetic or paramagnetic.

[0166] Various materials can be the source of or serve as samples for any method used in this disclosure. For example, samples can be or derived from: solid tissues, such as fresh, frozen, and / or preserved organ or tissue samples, biopsies, excisions, smears, or aspirates; scrapings; bone marrow or bone marrow specimens; primary or cultured cells or cell lines; tissue extracts; homogenates; tissue culture media; tumor lysates; cell lysates or extracts; bone marrow aspirates; blood or any blood component, such as whole blood, plasma, or serum; blood cells; body fluids, such as cerebrospinal fluid, vitreous fluid, amniotic fluid, lymph, synovial fluid, follicular fluid, semen, urine, saliva, sputum, breast milk, tears, sweat, mucus, etc. Fluids, peritoneal fluid, or tissue fluid; pleural fluid; ascites; tissue or fine-needle biopsy samples; platelets; surgical specimens; cellular body fluids; free-floating nucleic acids; feces; lymph; gynecological fluids; skin swabs; vaginal swabs; cervical swabs; oral swabs; nasal swabs; ear swabs; eye swabs; penile swabs; rectal swabs; throat swabs; urethral swabs; wound swabs; lavage fluids, such as catheter lavage fluid or bronchoalveolar lavage fluid; cells from any stage of pregnancy or development in an individual; cells from cancer or tumors; other body fluids, secretions, and / or excretions, and / or cells derived therefrom. In some embodiments, the sample is or comprises cells obtained from an individual. In some embodiments, the sample is or is derived from blood or blood components, such as from a liquid biopsy. In some embodiments, the sample is or is derived from a tumor sample. In some embodiments, the sample is or comprises biological tissue or fluid. In some embodiments, the sample may contain compounds that do not naturally mix with the sample source in nature, such as preservatives, anticoagulants, buffers, fixatives, nutrients, antibiotics, etc. In some embodiments, the sample is preserved as a frozen sample or a formalin or paraffin-embedded (FFPE) tissue preparation fixed in paraffin. In some embodiments, the sample contains circulating tumor cells (CTCs). In one embodiment, the sample is a liquid biopsy obtained from blood, plasma, cerebrospinal fluid, sputum, feces, urine, or saliva. In some embodiments, the sample contains cell-free DNA (cfDNA) and / or circulating tumor DNA (ctDNA), such as from a biopsy of blood, plasma, cerebrospinal fluid, sputum, feces, urine, or saliva. In another embodiment, the sample contains one or more circulating tumor cells (CTCs), such as CTCs obtained from a blood sample. In some embodiments, the sample is a raw sample obtained directly from the source of interest by any suitable means. For example, in some embodiments, the original biological sample is obtained by a method selected from biopsy (e.g., fine-needle aspiration or tissue biopsy), surgery, swabs, or body fluid collection (e.g., blood, lymph, or feces). In some embodiments, as will be clear from the context, the sample may be a preparation obtained by processing (e.g., by removing one or more components and / or by adding one or more reagents) the original sample.Such processed samples may contain, for example, nucleic acids or proteins extracted from a sample, or nucleic acids or proteins obtained by techniques such as amplification methods, mRNA reverse transcription, or isolation and / or purification of certain components such as nucleic acids and / or proteins from the original sample. In some embodiments, the sample contains nucleic acids, such as genomic DNA, cDNA, or mRNA. In some embodiments, the sample contains cell-free DNA (cfDNA). In some embodiments, the sample contains cell-free RNA (cfRNA). In some embodiments, the sample contains circulating tumor DNA (ctDNA). In some embodiments, the nucleic acids are purified or isolated (e.g., removed from their native state). In some embodiments, the sample is a control sample or a reference sample.

[0167] Any of the methods disclosed herein can be implemented on automated or robotic systems, such as automated or robotic fluid handling systems. The methods disclosed herein can also be implemented in microfluidic systems, for example using microfluidic chips or cartridges. Therefore, in some aspects, microfluidic devices, such as chips or cartridges, comprising or configured to receive the compositions disclosed herein are also provided.

[0168] V. Reagent kits and products

[0169] This document also provides kits or articles comprising any one or more compositions of this disclosure. In some embodiments, the kits or articles comprise microfluidic devices, such as chips or cartridges, that contain or are configured to receive compositions of this disclosure. In some embodiments, the compositions in the kits or articles may be disposed in a suitable container. Suitable containers include, for example, bottles, vials, tubes (e.g., screw tubes, microcentrifuge tubes, test tubes, conical tubes, etc.), ampoules, bags, cartridges (e.g., microfluidic cartridges, such as within a chamber of a cartridge), chips (e.g., microfluidic chips, such as within a chamber of a chip), syringes, cans, flexible packaging (e.g., sealed polyester film (Mylar) or plastic bags), etc. Containers may be formed of or comprise a variety of materials, such as glass or plastics (e.g., polypropylene, polyethylene, polypropylene copolymers, polymethylpentene, polyvinyl chloride, polyethylene terephthalate G copolymer, polycarbonate, polysulfone, polystyrene, or Teflon).

[0170] The kits or articles of this disclosure may include one or more additional components (e.g., disposed in one or more additional containers). Additional components may include, for example, diluents or buffers, such as water, phosphate-buffered saline, Ringer's solution, and / or glucose solution. The articles or kits of this disclosure may also include other materials desired from a commercial and user perspective, including additional buffers, diluents, filters, needles, magnets, and syringes. Additional components may be selected based on the intended use of the kit or article of manufacture or the compositions contained therein. For example, for cell lysis applications, the kit or article of manufacture may also include buffers (e.g., lysis buffer), surfactants, protease inhibitors, DNase inhibitors, RNase inhibitors, salts, metal ions, sugars, glycerol, metal chelators, reducing agents, etc., each disposed in one or more additional containers. In another instance, for analyte separation applications, the kit or product may also include buffers (e.g., lysis buffer, binding buffer, washing buffer, elution buffer), sample or specimen preservatives (e.g., Copan eNAT substrate), surfactants, protease inhibitors, DNase inhibitors, RNase inhibitors, salts, metal ions, sugars, glycerol, metal chelators, reducing agents, and reaction mixtures or reagents (e.g., PCR reaction mixtures or reagents, such as those containing buffers, salts, oligonucleotides, polymerases, reverse transcriptases, probes, or dyes).

[0171] In some embodiments, the kit or product of manufacture also includes information or instructions for use, such as for any of the uses described herein, for example, for isolating one or more analytes from a sample, for grinding or homogenizing tissue or samples, or for lysing one or more cells. The information or instructions may be in the form of a packaging insert or label. The information or instructions may take any form, such as paper or electronic media, such as magnetic recording media, CD-ROM, Universal Serial Bus (USB) flash drives, websites containing the information or instructions, software or applications (e.g., smartphone applications), etc.

[0172] This specification is considered sufficient to enable those skilled in the art to practice the invention. Various modifications to the invention, other than those shown and described herein, will become apparent to those skilled in the art from the foregoing description and fall within the scope of the appended claims. All publications, patents, and patent applications cited herein are incorporated herein by reference in their entirety for all purposes. In the event of any inconsistency between any reference incorporated by reference and this disclosure, this disclosure shall prevail.

[0173] This disclosure provides the following exemplary and non-limiting implementations: 1. A composition comprising a plurality of particles and (a) A mobile phase containing a suspending agent; (b) Viscosity enhancers; and (c) Solubilizer.

[0174] 2. The composition as described in Embodiment 1, wherein the concentration of the mobile phase is between about 60% and about 99%, between about 65% and about 95%, between about 70% and about 90%, between about 75% and about 90%, or between about 80% and about 90% (w / w) by weight.

[0175] 3. The composition as described in Embodiment 1 or Embodiment 2, wherein the concentration of the mobile phase is about 70%, about 80%, or about 90% w / w.

[0176] 4. The composition of any one of embodiments 1-3, wherein the concentration of the mobile phase is about 80% w / w.

[0177] 5. The composition of any one of embodiments 1-4, wherein the suspending agent is selected from the group consisting of sugar alcohols, glycols, water-miscible polymers, aprotic solvents, and any combination thereof.

[0178] 6. The composition of embodiment 5, wherein the sugar alcohol is selected from the group consisting of glycerol, sorbitol, erythritol, threitol, arabinitol, xylitol, ribitol, mannitol, galactitol, fucitol, idotitol, inositol, heptetol, isomaltitol, maltitol, lactitol, maltotriol, maltotetratitol, polyglycol, and any combination thereof.

[0179] 7. The composition as described in Embodiment 6, wherein the sugar alcohol is glycerol.

[0180] 8. The composition as described in Example 7, wherein the concentration of glycerol in the composition is about 80% w / w.

[0181] 9. The composition of any one of embodiments 5-8, wherein the diol is selected from the group consisting of diethylene glycol, ethylene glycol, hexanediol, propylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, glycol ethers, and any combination thereof.

[0182] 10. The composition as described in Embodiment 9, wherein the diol is propylene glycol.

[0183] 11. The composition of any one of embodiments 5-10, wherein the water-miscible polymer is selected from the group consisting of: acrylic polymers, ether polymers, epoxy polymers, polyethylene polymers, polyethylene glycol polymers, polystyrene polymers, polyvinyl chloride polymers, polytetrafluoroethylene polymers, polydimethylsiloxane polymers, polyester polymers, poly(N-vinylpyrrolidone) polymers, polystyrene copolymers, polyurethane polymers, and any combination thereof.

[0184] 12. The composition of embodiment 11, wherein the water-miscible polymer is a polyethylene glycol (PEG) polymer.

[0185] 13. The composition of any one of embodiments 5-12, wherein the water-miscible polymer comprises an average molecular weight of about 1000 g / mol or less, about 900 g / mol or less, about 800 g / mol or less, about 700 g / mol or less, about 600 g / mol or less, about 500 g / mol or less, about 400 g / mol or less, about 300 g / mol or less, about 200 g / mol or less, or about 100 g / mol or less.

[0186] 14. The composition of any one of embodiments 5-12, wherein the water-miscible polymer comprises an average molecular weight between about 100 g / mol and about 1000 g / mol, between about 200 g / mol and about 600 g / mol, between about 200 g / mol and about 400 g / mol, or between about 200 g / mol and about 300 g / mol.

[0187] 15. The composition of any one of embodiments 5-12, wherein the water-miscible polymer comprises an average molecular weight of about 200 g / mol or about 300 g / mol.

[0188] 16. The composition of any one of embodiments 5-15, wherein the water-miscible polymer is PEG 200 and / or PEG 300.

[0189] 17. The composition of any one of embodiments 5-16, wherein the aprotic solvent is a polar aprotic solvent, optionally a dipole aprotic solvent.

[0190] 18. The composition of embodiment 17, wherein the aprotic solvent is selected from the group consisting of dimethyl sulfoxide (DMSO), dimethyl sulfone, diphenyl sulfone (DPS), diethyl sulfoxide, diethyl sulfone, diisopropyl sulfone, sulfolane, tetrahydrothiophene-1-monoxide, N,N-dimethylacetamide (DMAc), N,N-dimethylformamide (DMF), N-methyl-2-pyrrolidone (NMP), and any combination thereof.

[0191] 19. The composition as described in Embodiment 18, wherein the aprotic solvent is sulfolane.

[0192] 20. The composition of any one of embodiments 1-19, wherein the viscosity enhancer is at least partially soluble in the mobile phase.

[0193] 21. The composition of any one of embodiments 1-20, wherein the concentration of the viscosity enhancer is between about 1% and about 40%, between about 1% and about 35%, between about 1% and about 30%, between about 1% and about 25%, between about 1% and about 20%, between about 1% and about 15%, between about 1% and about 10%, or between about 1% and about 5% w / w.

[0194] 22. The composition of any one of embodiments 1-20, wherein the concentration of the viscosity enhancer is about 5% w / w.

[0195] 23. The composition of any one of embodiments 1-22, wherein the viscosity enhancer comprises a water-miscible polymer.

[0196] 24. The composition of embodiment 23, wherein the water-miscible polymer comprises an average molecular weight of at least about 2000 g / mol, at least about 4000 g / mol, at least about 5000 g / mol, at least about 6000 g / mol, at least about 7000 g / mol, at least about 8000 g / mol, at least about 9000 g / mol, at least about 10000 g / mol, at least about 12000 g / mol, at least about 14000 g / mol, at least about 16000 g / mol, at least about 18000 g / mol, at least about 20000 g / mol, at least about 25000 g / mol, or at least about 30000 g / mol.

[0197] 25. The composition of embodiment 23, wherein the water-miscible polymer comprises an average molecular weight between about 2000 g / mol and about 30000 g / mol, between about 4000 g / mol and about 20000 g / mol, between about 4000 g / mol and about 10000 g / mol, or between about 4000 g / mol and about 8000 g / mol.

[0198] 26. The composition of embodiment 23, wherein the water-miscible polymer comprises an average molecular weight of about 4000 g / mol, about 8000 g / mol, about 10000 g / mol, or about 20000 g / mol.

[0199] 27. The composition of any one of embodiments 23-26, wherein the water-miscible polymer is selected from the group consisting of: acrylic polymers, ether polymers, epoxy polymers, polyethylene polymers, polyethylene glycol polymers, polystyrene polymers, polyvinyl chloride polymers, polytetrafluoroethylene polymers, polydimethylsiloxane polymers, polyester polymers, poly(N-vinylpyrrolidone) polymers, polystyrene copolymers, polyurethane polymers, and any combination thereof.

[0200] 28. The composition of embodiment 27, wherein the water-miscible polymer comprises a polyethylene glycol (PEG) polymer.

[0201] 29. The composition of embodiment 28, wherein the PEG polymer is selected from the group consisting of PEG 4000, PEG8000, PEG 10000, PEG 20000 and any combination thereof.

[0202] 30. The composition of embodiment 29, wherein the PEG polymer is PEG 8000.

[0203] 31. The composition as described in Example 30, wherein the concentration of PEG 8000 in the composition is about 5% w / w.

[0204] 32. The composition of any one of embodiments 1-22, wherein the viscosity enhancer comprises polyvinyl alcohol (PVA).

[0205] 33. The composition of any one of embodiments 1-22, wherein the viscosity enhancer comprises sulfone or a sulfone polymer.

[0206] 34. The composition of any one of embodiments 1-33, wherein the solubilizer is at least partially soluble in the mobile phase.

[0207] 35. The composition of any one of embodiments 1-34, wherein the solubilizer is water-soluble.

[0208] 36. The composition of any one of embodiments 1-35, wherein the concentration of the solubilizer is between about 1% and about 40%, between about 5% and about 30%, between about 10% and about 25%, or between about 10% and about 20% w / w.

[0209] 37. The composition of any one of embodiments 1-36, wherein the concentration of the solubilizer is about 15% w / w.

[0210] 38. The composition of any one of embodiments 1-37, wherein the solubilizer comprises a liquid-dissolving agent.

[0211] 39. The composition of embodiment 38, wherein the liquid release agent is selected from the group consisting of: n-butanol, ethanol, guanidine salts, lithium perchlorate, lithium acetate, magnesium chloride, phenol, 2-propanol, sodium dodecyl sulfate, thiourea, urea, water-soluble urea derivatives, and any combination thereof.

[0212] 40. The composition of embodiment 39, wherein the liquid release agent is a guanidine salt.

[0213] 41. The composition of embodiment 40, wherein the guanidine salt is selected from the group consisting of guanidine chloride, guanidine sulfate, guanidine carbonate, guanidine nitrate, guanidine isothiocyanate, guanidine thiocyanate, and any combination thereof.

[0214] 42. The composition of embodiment 39, wherein the liquid release agent is urea and / or a water-soluble urea derivative.

[0215] 43. The composition of embodiment 42, wherein the concentration of urea and / or water-soluble urea derivative in the composition is about 15% w / w.

[0216] 44. The composition of any one of embodiments 42-43, wherein the water-soluble urea derivative is thiourea, hydroxyurea, dimethylurea, or any combination thereof.

[0217] 45. The composition of any one of embodiments 1-44, wherein the solubilizer comprises a buffer.

[0218] 46. ​​The composition of embodiment 45, wherein the buffer is selected from the group consisting of: MES, Bis-Tris, ADA, ACES, PIPES, MOPSO, Bis-Tris propane, BES, MOPS, TES, HEPES, DIPSO, MOBS, TAPSO, Tris, HEPPSO, POPSO, TEA, EPPS, HEPPS, Tricine, Gly-Gly, Bicine, HEPBS, TAPS, AMPD, TABS, AMPSO, CHES, CAPSO, AMP, CAPS, CABS, phosphate, maleate, glycine, citrate, formate, succinate, acetate, propionate, pyridine, piperazine, carcoate, histidine, ethanolamine, carbonate, imidazole, pyrophosphate, hydrazine, taurine (AES), borate, ammonium hydroxide, methylamine, piperidine, malate buffer, and any combination thereof.

[0219] 47. The composition of embodiment 46, wherein the buffer comprises TAPS, HEPES or MOPS buffer or any combination thereof.

[0220] 48. The composition of any one of embodiments 1-8, 20-31, 34-39 and 42-43, wherein the suspending agent comprises glycerol, the viscosity enhancer comprises PEG 8000, and the solubilizer comprises urea.

[0221] 49. The composition of embodiment 48, wherein the concentration of glycerol is about 80% w / w, the concentration of PEG8000 is about 5% w / w, and the concentration of urea is about 15% w / w.

[0222] 50. The composition as described in Embodiment 48 or Embodiment 49, wherein the ratio of glycerol:PEG8000:urea in the composition is 16:1:3 w / w.

[0223] 51. The composition of any one of embodiments 1-50, wherein the pH of the composition is between about 7 and about 8.

[0224] 52. The composition according to any one of embodiments 1-51, wherein the composition has the following viscosity: (a) When measured at a temperature of about 15°C, between about 7000 mPa·s and about 8000 mPa·s, between about 7250 mPa·s and about 8000 mPa·s, between about 7500 mPa·s and about 8000 mPa·s, or between about 7750 mPa·s and about 8000 mPa·s; (b) When measured at a temperature of about 20°C, between about 5000 mPa·s and about 6000 mPa·s, between about 5250 mPa·s and about 6000 mPa·s, between about 5500 mPa·s and about 6000 mPa·s, or between about 5500 mPa·s and about 5750 mPa·s; (c) When measured at a temperature of about 25°C, the values ​​are between about 5500 mPa·s and about 7000 mPa·s, between about 5750 mPa·s and about 6750 mPa·s, or between about 6000 mPa·s and about 6500 mPa·s. (d) When measured at a temperature of about 30°C, between about 4250 mPa·s and about 5500 mPa·s, between about 4500 mPa·s and about 5500 mPa·s, between about 4750 mPa·s and about 5250 mPa·s, or between about 4750 mPa·s and about 5000 mPa·s; (e) When measured at a temperature of about 35°C, the values ​​are between about 2000 mPa·s and about 3000 mPa·s, between about 2250 mPa·s and about 2750 mPa·s, or between about 2250 mPa·s and about 2500 mPa·s. (f) When measured at a temperature of about 40°C, between about 750 mPa·s and about 1750 mPa·s, between about 1000 mPa·s and about 1750 mPa·s, or between about 1000 mPa·s and about 1500 mPa·s. (g) When measured at a temperature of about 45°C, the values ​​are between about 500 mPa·s and about 1500 mPa·s, between about 750 mPa·s and about 1250 mPa·s, or between about 1000 mPa·s and about 1250 mPa·s. (h) When measured at a temperature of about 50°C, between about 250 mPa·s and about 1500 mPa·s, between about 500 mPa·s and about 1250 mPa·s, or between about 500 mPa·s and about 1000 mPa·s. (i) When measured at a temperature of about 55°C, the values ​​are between about 500 mPa·s and about 1500 mPa·s, between about 750 mPa·s and about 1250 mPa·s, or between about 1000 mPa·s and about 1250 mPa·s; and / or (j) When measured at a temperature of about 60°C, between about 100 mPa·s and about 600 mPa·s, between about 200 mPa·s and about 500 mPa·s, or between about 200 mPa·s and about 400 mPa·s.

[0225] 53. The composition as described in embodiment 52, wherein the viscosity of the composition is evaluated using a rotational viscometer.

[0226] 54. The composition as described in embodiment 53, wherein the viscosity of the composition is evaluated at a shaft rotation speed of about 10 revolutions per minute (RPM).

[0227] 55. The composition of any one of embodiments 1-54, wherein the density of the composition is between about 0.5 g / mL and about 2 g / mL, between about 1 g / mL and about 2 g / mL, between about 1 g / mL and about 1.5 g / mL, or between about 1.1 g / mL and about 1.5 g / mL.

[0228] 56. The composition of any one of embodiments 1-55, wherein the density of the composition is about 1.3 g / mL.

[0229] 57. The composition as described in any one of embodiments 55-56, wherein the density of the composition is evaluated on an analytical balance.

[0230] 58. The composition of any one of embodiments 1-57, wherein the mobile phase is non-aqueous or substantially non-aqueous.

[0231] 59. The composition of any one of embodiments 1-58, wherein the composition is non-aqueous or substantially non-aqueous.

[0232] 60. The composition of any one of embodiments 1-59, wherein the water content of the composition is about 1% or less.

[0233] 61. The composition as described in embodiment 60, wherein the water content of the composition is assessed by Karl Fischer titration.

[0234] 62. The composition of any one of embodiments 1-61, wherein the composition is a liquid composition.

[0235] 63. The composition of any one of embodiments 1-62, wherein the plurality of particles comprises one or more particles configured to bind nucleic acids, peptides, lipids, carbohydrates or small molecules.

[0236] 64. The composition of embodiment 63, wherein the plurality of particles comprises one or more particles configured to bind DNA and / or RNA.

[0237] 65. The composition of any one of embodiments 1-64, wherein the plurality of particles comprises one or more microparticles, nanoparticles, microspheres, paramagnetic beads, magnetic beads, microbeads, nanobeads or any combination thereof.

[0238] 66. The composition of any one of embodiments 1-65, wherein the plurality of particles comprises one or more silica beads, silica gel beads, controllable porosity glass beads, magnetic beads, glass beads, paramagnetic beads, immunomagnetic beads, Sephadex / Sepharose beads, cellulose beads, polystyrene beads, mineral beads, crystalline particles, zircon particles, zirconite particles, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof.

[0239] 67. The composition of any one of embodiments 1-66, wherein one or more of the plurality of particles are functionalized, optionally wherein the one or more particles are surface functionalized with carboxyl, amino, hydroxyl, silica, streptavidin, endopeptidase moiety, amine, thiol, glycol, polymer, antibody or antibody fragment, nucleic acid, oligonucleotide, peptide, polypeptide or any combination thereof.

[0240] 68. The composition as described in embodiment 66 or embodiment 67, wherein the plurality of particles comprise magnetic silica beads.

[0241] 69. The composition of any one of embodiments 1-68, wherein the plurality of particles are present in the composition at a concentration of at least about 0.5%, at least about 1%, at least about 2.5%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 30% by weight / volume (w / v).

[0242] 70. The composition of any one of embodiments 1-68, wherein the plurality of particles are present in the composition at a concentration between about 0.5% and about 30% w / v, between about 1% and about 25% w / v, between about 2.5% and about 20% w / v, or between about 5% and about 15% w / v.

[0243] 71. The composition of any one of embodiments 1-68, wherein the plurality of particles are present in the composition at a concentration of about 10% w / v.

[0244] 72. The composition of any one of embodiments 1-71, wherein the composition enhances the stability of particles among a plurality of particles compared to corresponding particles in an aqueous solution.

[0245] 73. The composition of any one of embodiments 1-72, wherein the plurality of particles in the composition are stable for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months.

[0246] 74. The composition as described in Embodiment 72 or Embodiment 73, wherein particle stability is assessed based on particle integrity, particle aggregation, and / or retention of ligand binding capacity.

[0247] 75. The composition of any one of embodiments 1-74, wherein, compared to a baseline, the particles of the plurality of particles retain at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 80%, at least about 90%, at least about 90%, at least about 95%, or at least about 99% ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% of the ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 8 months, at least about 9 months, at least about 90%, at least about 95%, or at least about 99% of the ligand binding capacity.

[0248] 76. The composition of any one of embodiments 1-75, wherein the composition enhances the ligand binding of the particles in the plurality of particles by at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% compared to the corresponding particles in the aqueous solution.

[0249] 77. The composition of any one of embodiments 1-76, wherein the plurality of particles comprise particles capable of binding nucleic acid ligands.

[0250] 78. The composition of embodiment 77, wherein the stability of the particles is assessed based on their nucleic acid ligand binding capacity compared to a baseline and / or to corresponding particles in an aqueous solution.

[0251] 79. The composition as described in Embodiment 77 or Embodiment 78, wherein the nucleic acid ligand comprises DNA and / or RNA.

[0252] 80. The composition of any one of embodiments 77-79, wherein the plurality of particles comprise silica particles, optionally magnetic silica particles.

[0253] 81. The composition of any one of embodiments 77-80, wherein, compared to a baseline, the particles of the plurality of particles retain at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99% of their nucleic acid ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 99% of their nucleic acid ligand binding capacity for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months.

[0254] 82. The composition of any one of embodiments 77-81, wherein the composition enhances the binding of nucleic acid ligands of the particles in the plurality of particles by at least about 1%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 55%, at least about 60%, at least about 65%, at least about 70%, at least about 75%, at least about 80%, at least about 85%, at least about 90%, at least about 95%, or at least about 100% compared to the corresponding particles in the aqueous solution.

[0255] 83. The composition as described in any one of embodiments 72-82, wherein particle stability is evaluated at room temperature.

[0256] 84. The composition of any one of embodiments 72-83, wherein particle stability is evaluated at a temperature between about 20°C and about 30°C.

[0257] 85. The composition as described in Example 84, wherein particle stability is evaluated at a temperature of about 25°C.

[0258] 86. The composition of any one of embodiments 72-85, wherein particle stability is evaluated under normal atmospheric conditions, under low oxygen conditions, or in nitrogen.

[0259] 87. The composition of any one of embodiments 1-86, wherein the composition is capable of adhering to a polypropylene surface.

[0260] 88. The composition of any one of embodiments 1-87, wherein the composition has microbiological stability for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months.

[0261] 89. The composition of any one of embodiments 1-88, wherein the composition further comprises a reagent selected from the group consisting of antioxidants, reducing agents, chelating agents, and any combination thereof.

[0262] 90. The composition of any one of embodiments 1-89, wherein the composition does not contain an antimicrobial agent.

[0263] 91. The composition of any one of embodiments 1-90, wherein the composition contains less than about 10% surfactant or detergent.

[0264] 92. The composition of any one of embodiments 1-91, wherein the composition does not contain surfactants or detergents.

[0265] 93. A method for preparing a composition comprising a plurality of particles, the method comprising: (a) Provide multiple particles; and (b) Suspending the plurality of particles in a formulation containing the following substances: i. A mobile phase containing a suspending agent; ii. Viscosity enhancers; and iii. Solubilizer.

[0266] 94. The method as described in embodiment 93, wherein the plurality of particles provided in step (a) are dehydrated or freeze-dried.

[0267] 95. The method of embodiment 94, wherein the method further comprises dehydrating or freeze-drying the plurality of particles prior to step (a).

[0268] 96. The method of embodiment 95, wherein the dehydration comprises suspending the plurality of particles in a first organic solvent.

[0269] 97. The method as described in Embodiment 95 or Embodiment 96, wherein the dehydration comprises: (i) separating a plurality of particles stored in an aqueous solution from the aqueous solution, and (ii) suspending the separated plurality of particles in a first volume of a first organic solvent.

[0270] 98. The method of embodiment 97, wherein the dehydration further comprises: (1) separating a plurality of particles from a first organic solvent, and (2) resuspending the separated plurality of particles in another volume of the first organic solvent.

[0271] 99. The method as described in embodiment 98 includes repeating steps (1) and (2) at least once, at least twice, or more.

[0272] 100. The method of embodiment 95 or embodiment 96, wherein the dehydration comprises: (i) separating a plurality of particles stored in an aqueous solution from the aqueous solution, and (ii) suspending the separated plurality of particles in a series of volumes of a first organic solvent, wherein the volumes in the series contain an increased amount of the first organic solvent, wherein the first volume in the series contains an organic solvent concentration between about 20% and about 80%, and the last volume in the series contains an organic solvent concentration of about 100%.

[0273] 101. The method of embodiment 100, wherein the first volume of the series of volumes contains about 50% organic solvent concentration, and the last volume of the series of volumes contains about 100% organic alcohol concentration.

[0274] 102. The method as described in embodiment 100 or embodiment 101, wherein the series of volumes comprises about 2 to about 15 volumes, about 2 to about 10 volumes, or about 5 to about 7 volumes.

[0275] 103. The method of any one of embodiments 96-102, wherein the first organic solvent comprises an organic solvent that is miscible with water and / or has high solubility in water.

[0276] 104. The method of any one of embodiments 96-103, wherein the first organic solvent comprises: Polar aprotic solvent, optionally said polar aprotic solvent is DMSO, tetrahydrofuran (THF), acetonitrile, propylene carbonate, sulfolane, and any combination thereof; A water-miscible P-type or E-type glycol ether, wherein the first organic solvent optionally comprises dipropylene glycol methyl ether and / or diethylene glycol ethyl ether; Alcohol, optionally said alcohol being ethanol and / or isopropanol; Tetrahydrothiophene 1-monoxide; Or any combination thereof.

[0277] 105. The method of any one of embodiments 96-104, wherein the first organic solvent comprises a mixture of two or more solvents, optionally wherein the solvents are in a ratio of about 1:1, and further optionally wherein the mixture comprises: DMSO and ethanol; DMSO and isopropanol; or DMSO and THF.

[0278] 106. The method of any one of embodiments 96-105, wherein the first organic solvent comprises DMSO.

[0279] 107. The method of any one of embodiments 100-106, wherein the first organic solvent comprises an alcohol, optionally wherein the alcohol is ethanol and / or isopropanol.

[0280] 108. The method of any one of embodiments 96-107, wherein step (b) comprises: (i) separating a plurality of particles from a first organic solvent of a given volume, and (ii) suspending the separated plurality of particles in a given volume of the formulation.

[0281] 109. The method of any one of embodiments 93-107, further comprising, prior to step (b), suspending a plurality of particles in a first volume of solution, said solution comprising: The second organic solvent, and Suspension agent.

[0282] 110. The method of any one of embodiments 96-109, wherein the method further comprises, prior to step (b): (i) separating a plurality of particles from a first organic solvent of a given volume, and (ii) suspending the separated plurality of particles in a first volume of solution, said solution comprising: The second organic solvent, and Suspension agent.

[0283] 111. The method as described in Embodiment 109 or Embodiment 110 further comprises: (1) separating the plurality of particles from the solution, and (2) resuspending the separated plurality of particles in another volume of the solution.

[0284] 112. The method as described in embodiment 111 includes repeating steps (1) and (2) at least once, at least twice, or more.

[0285] 113. The method of any one of embodiments 109-112, wherein the second organic solvent and the suspending agent in the solution are in a ratio of about 1:1.

[0286] 114. The method of any one of embodiments 109-113, wherein the suspending agent is selected from the group consisting of sugar alcohols, glycols, water-miscible polymers, aprotic solvents, and any combination thereof.

[0287] 115. The method as described in embodiment 114, wherein: The sugar alcohol is selected from the group consisting of glycerol, sorbitol, erythritol, threitol, arabinitol, xylitol, ribitol, mannitol, galactitol, fucitol, idotitol, inositol, heptacaphexol, isomaltitol, maltitol, lactitol, maltotriol, maltotetratitol, polyglycol, and any combination thereof, optionally wherein the sugar alcohol is glycerol; The diol is selected from the group consisting of: diethylene glycol, ethylene glycol, hexanediol, propylene glycol, dipropylene glycol, triethylene glycol, tripropylene glycol, glycol ethers, and any combination thereof; optionally, the diol is propylene glycol. The water-miscible polymer is selected from the group consisting of: acrylic polymers, ether polymers, epoxy polymers, polyethylene polymers, polyethylene glycol polymers, polystyrene polymers, polyvinyl chloride polymers, polytetrafluoroethylene polymers, polydimethylsiloxane polymers, polyester polymers, poly(N-vinylpyrrolidone) polymers, polystyrene copolymers, polyurethane polymers, and any combination thereof, optionally wherein the water-miscible polymer is PEG 200 and / or PEG 300; and / or The aprotic solvent is a polar aprotic solvent, and optionally the aprotic solvent is sulfolane.

[0288] 116. The method of embodiment 115, wherein the suspending agent comprises glycerol.

[0289] 117. The method of any one of embodiments 109-116, wherein the second organic solvent comprises an organic solvent that is miscible with water and / or has high solubility in water.

[0290] 118. The method of any one of embodiments 109-117, wherein the second organic solvent comprises: Polar aprotic solvent, optionally said polar aprotic solvent is DMSO, tetrahydrofuran (THF), acetonitrile, propylene carbonate, sulfolane, and any combination thereof; A water-miscible P- or E-type glycol ether, wherein the second organic solvent optionally comprises dipropylene glycol methyl ether and / or diethylene glycol ethyl ether; Alcohol, optionally said alcohol is ethanol and / or isopropanol; or Tetrahydrothiophene 1-oxide

[0291] 119. The method of any one of embodiments 109-118, wherein the second organic solvent comprises a mixture of two or more solvents, optionally wherein the solvents are in a ratio of about 1:1, and further optionally wherein the mixture comprises: DMSO and ethanol; DMSO and isopropanol; or DMSO and THF.

[0292] 120. The method of any one of embodiments 109-119, wherein the second organic solvent comprises DMSO.

[0293] 121. The method of any one of embodiments 109-120, wherein: (1) the second organic solvent is the same as the first organic solvent; or (2) the second organic solvent is different from the first organic solvent.

[0294] 122. The method of embodiment 121, wherein the first and second organic solvents comprise DMSO.

[0295] 123. The method of any one of embodiments 109-122, wherein step (b) comprises: (i) separating a plurality of particles from a volume of the solution comprising a second organic solvent and a suspending agent, and (ii) suspending the separated plurality of particles in a volume of the formulation.

[0296] 124. A composition comprising a plurality of particles, said composition being produced by any one of embodiments 93-123.

[0297] 125. A method for separating an analyte from a sample, comprising: (a) Provide a sample containing the analyte; (b) The sample is mixed with a composition comprising multiple particles as described in any one of Embodiments 1-92 and 124, or a composition comprising multiple particles produced by any one of Embodiments 93-123, to produce a mixture of the sample and the composition, thereby binding the analyte to one or more of the multiple particles; and (c) Separating multiple particles from the mixture.

[0298] 126. The method of embodiment 125 further includes eluting analytes bound to one or more of the plurality of particles, and optionally separating the plurality of particles from the eluted analytes.

[0299] 127. The method of embodiment 126 further includes separating or recovering the eluted analytes.

[0300] 128. The method of any one of embodiments 125-127, wherein the analyte is a nucleic acid, polypeptide, lipid, carbohydrate, or small molecule, and optionally wherein the nucleic acid is DNA and / or RNA.

[0301] 129. The method of any one of embodiments 125-128, wherein the plurality of particles comprises one or more particles configured to bind DNA and / or RNA.

[0302] 130. The method of any one of embodiments 125-129, wherein the plurality of particles comprises one or more microparticles, nanoparticles, microspheres, paramagnetic beads, magnetic beads, microbeads, nanobeads or any combination thereof.

[0303] 131. The method of any one of embodiments 125-130, wherein the plurality of particles comprises one or more silica beads, silica gel beads, controllable porosity glass beads, magnetic beads, glass beads, paramagnetic beads, immunomagnetic beads, Sephadex / Sepharose beads, cellulose beads, polystyrene beads, mineral beads, crystalline particles, zircon particles, zirconite particles, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof.

[0304] 132. The method of any one of embodiments 125-131, wherein one or more of the plurality of particles are functionalized, optionally wherein the one or more particles are surface functionalized with carboxyl, amino, hydroxyl, silica, streptavidin, endopeptidase moiety, amine, thiol, glycol, polymer, antibody or antibody fragment, nucleic acid, oligonucleotide, peptide, polypeptide or any combination thereof.

[0305] 133. The method as described in embodiment 131 or 132, wherein the plurality of particles comprise silica beads, optionally magnetic silica beads, and further optionally wherein the analyte is DNA and / or RNA.

[0306] 134. The method of any one of embodiments 125-132, wherein the sample is or is derived from tissue, primary or cultured cells or cell lines, cell supernatant, cell lysate, platelets, serum, plasma, vitreous fluid, lymph, synovial fluid, follicular fluid, semen, amniotic fluid, breast milk, whole blood, blood-derived cells, urine, cerebrospinal fluid, saliva, sputum, tears, sweat, mucus, tumor lysate, tissue culture medium, tissue extract, homogenate tissue, tumor tissue, cell extract, or a combination thereof.

[0307] 135. The method of any one of embodiments 125-132, wherein the sample is a liquid biopsy sample, optionally wherein the liquid biopsy sample is a blood or plasma sample.

[0308] 136. The method of embodiment 135, wherein the sample is a liquid biopsy sample and the analyte is cell-free DNA or cell-free RNA.

[0309] 137. The method of any one of embodiments 125-132, wherein the sample is or is derived from a nasal swab, oral swab, cervical swab, ear swab, eye swab, vaginal swab, penile swab, rectal swab, throat swab, urethral swab, vulvar swab, wound swab, or skin swab.

[0310] 138. A method for cell lysis, comprising: (a) Provide a sample containing multiple cells; (b) The sample is mixed with the composition comprising multiple particles as described in any one of Embodiments 1-92 and 124, or with the composition comprising multiple particles produced by the method described in any one of Embodiments 93-123, thereby producing a mixture of the sample and the composition; and (c) Stir the mixture to lyse one or more cells in the plurality of cells.

[0311] 139. The method of embodiment 138 further includes separating the plurality of particles from the mixture.

[0312] 140. The method as described in embodiment 138 or embodiment 139, wherein the one or more cells comprise one or more prokaryotic cells and / or one or more eukaryotic cells.

[0313] 141. The method of any one of embodiments 138-140, wherein the one or more cells comprise one or more animal cells, plant cells, mammalian cells, bacterial cells, archaea cells, fungal cells, protozoan cells, algal cells, or any combination thereof.

[0314] 142. The method of any one of embodiments 138-141, wherein the plurality of particles comprises one or more mineral beads, crystalline particles, zircon particles, zircon stones, zirconium silicate particles, zirconium oxide particles, zirconium dioxide particles, quartz particles, alumina particles, silicon carbide particles, ceramic particles, glass particles, silica glass particles, silica particles, metal particles, steel particles, stainless steel particles, yttrium particles, chromium steel particles, or any combination thereof.

[0315] 143. The method of any one of embodiments 125-142, wherein the method is implemented on a microfluidic device and / or an automated or robotic liquid handling system.

[0316] 144. A kit comprising the composition of any one of embodiments 1-92 and 124, or the composition produced by any one of embodiments 93-123.

[0317] 145. The kit as described in Embodiment 144 further includes instructions for using the composition to separate one or more analytes from a sample, optionally wherein the instructions are for separating one or more analytes from a sample according to the method of any one of Embodiments 125-137 and 143.

[0318] 146. The kit as described in Embodiment 144 further includes instructions for using the composition to lyse one or more cells from a sample, optionally wherein the instructions are for lysing one or more cells according to any one of Embodiments 138-143.

[0319] 147. A microfluidic device comprising the composition of any one of embodiments 1-92 and 124, or a liquid composition produced by any one of embodiments 93-123.

[0320] Example

[0321] The invention will be more fully understood by referring to the following embodiments. However, they should not be construed as limiting the scope of the invention. It should be understood that the embodiments and implementations described herein are for illustrative purposes only, and those skilled in the art will suggest various modifications or changes based thereon, and such modifications or changes are included within the spirit and scope of this application and the appended claims.

[0322] Example 1: Development of formulations for enhancing particle stability and processing.

[0323] Parts, such as magnetic beads, are widely used in many applications in molecular biology. For example, magnetic silica beads are frequently used to isolate DNA and RNA. Parts are typically stored as dried compositions or aqueous suspensions. However, drying particles can lead to particle aggregation or degradation, as well as resuspension issues. Aqueous suspensions of particles allow for sedimentation, which can lead to aggregation and clumping, and require continuous mixing to ensure consistency during use. This embodiment describes the development of candidate liquid formulations with high viscosity and density to enhance particle stability and handling.

[0324] Materials and methods

[0325] Preparation of candidate formulations

[0326] A three-step method was used to prepare the candidate particle liquid formulation. Magnetic silica beads used for nucleic acid isolation were used as exemplary particles in the candidate liquid formulation.

[0327] As detailed below, in the first step, the silica beads are dehydrated using an organic solvent to remove the aqueous buffer solution present when the beads are received from the manufacturer. After dehydration, the amount of organic solvent is reduced, and the viscosity of the bead mixture is increased. Finally, the candidate formulation is prepared by resuspending the dehydrated beads in a solution containing the mobile phase, viscosity enhancer, and excipients.

[0328] (1) Dehydration of beads

[0329] The exemplary magnetic silica beads used in this embodiment were received from the manufacturer in an aqueous suspension buffer. To remove the buffer and prepare the beads for subsequent steps, the beads were first dehydrated using an organic solvent as described below: 1. Transfer the mixture of beads in aqueous suspension buffer to a square weighing boat.

[0330] 2. Place the magnet under the weighing boat for at least 30 seconds to separate the beads from the suspension buffer.

[0331] 3. Remove the suspension buffer from the beads by pipetting.

[0332] 4. Add the organic solvent to the beads on the weighing boat and mix thoroughly with a glass rod at least 6 times, repeating until a uniform consistency is obtained.

[0333] 5. Repeat steps 2-4 at least twice more.

[0334] 6. Remove the organic solvent by placing a magnet under the weighing boat for at least 30 seconds to separate the beads from the solvent. Then remove the solvent by pipetting to obtain dehydrated beads, ready for the next step in the process.

[0335] Several organic solvents were tested during the dehydration step, including those listed in Table 1.

[0336] Table 1. Candidate organic solvents for bead formulation.

[0337]

[0338] (2) Reduce solvent content and initially increase viscosity

[0339] To reduce the amount of solvent that may evaporate in the final formulation and to increase the viscosity of the bead mixture, the dehydrated beads were washed in a 1:1 mixture of organic solvent and glycerol as described below: 1. Add a 1:1 mixture of organic solvent and glycerin to the dehydration beads on the weighing boat and mix thoroughly with a glass rod at least 6 times, repeating until a uniform consistency is obtained.

[0340] 2. Place the magnet under the weighing boat for at least 30 seconds to separate the beads from the solvent and glycerin mixture.

[0341] 3. Remove the solvent and glycerol mixture by pipetting.

[0342] 4. Repeat steps 1-3 at least once.

[0343] Several organic solvents were tested in this step, including those listed in Table 1 above.

[0344] (3) Candidate formulations

[0345] Candidate formulations containing various combinations of mobile phase, viscosity enhancer, and excipients were prepared. The reagents listed in Table 2 were tested.

[0346] Table 2. Reagents used for testing candidate formulations.

[0347]

[0348] To prepare the candidate formulation, the beads were resuspended in a candidate solution containing a combination of mobile phase, viscosity enhancer, and excipients, as described below: 1. Use a sterile Pasteur pipette to add the candidate solution into the bead.

[0349] 2. Use a glass rod to thoroughly mix the solution and beads at least 6 times, repeating until a uniform consistency is obtained.

[0350] Stability, functionality and viscosity testing

[0351] The stability, functionality, and viscosity of the beads were evaluated to determine the suitability of the candidate reagents tested in steps 1-3 above.

[0352] Stability: The stability of the beads is determined based on their functional performance.

[0353] Functionality: The functionality of the beads is determined based on their ability to retain nucleic acid binding using fluorescence analysis. In short, a known amount of RNA is mixed with the beads, washed, and eluted. The amount of RNA eluted is then quantified using fluorescence assays (Quantus, Promega) according to the manufacturer's instructions. If a decrease in nucleic acid binding efficiency of 10% or more is observed, the candidate reagent is considered incompatible.

[0354] Viscosity: The viscosity of the candidate formulations tested in step 3 above was evaluated based on their adhesion to the polypropylene surface and their ability to transfer the formulation.

[0355] result

[0356] organic solvents

[0357] Testing of the candidate organic solvents in Table 1 showed that polar aprotic solvents, such as DMSO, THF, acetonitrile, and propylene carbonate, were effective at dehydrating the beads without causing degradation, aggregation, or loss of nucleic acid binding capacity, and did not require extensive washing. Alcohols, such as ethanol and isopropanol, were also effective, but required a more refined or controlled dehydration process (see Table 3 below). Water-miscible p- and e-type glycol ethers (e.g., dipropylene glycol methyl ether and diethylene glycol ethyl ether), as well as 1:1 mixtures of DMSO and ethanol, DMSO and isopropanol, and THF and DMSO, were also suitable. Table 3 below provides a summary of suitable candidate solvents.

[0358] Table 3: Suitable organic solvents.

[0359]

[0360] The following organic solvents were found to cause particle degradation, aggregation, or loss of function, or to prevent adequate dehydration under test conditions: dichloromethane Chloroform Toluene Isoamyl alcohol 2-Phenoxyethanol Acetic acid (leads to partial degradation of beads) In summary, the results indicate that solvents miscible with water or with high solubility in water (e.g., propylene carbonate) are suitable for the dehydration of beads. Solvents immiscible with water or with low water solubility (e.g., 2-phenoxyethanol) may not adequately dehydrate the particles or may lead to degradation, aggregation, or loss of bead function.

[0361] Components in candidate formulations

[0362] Candidate formulations containing various combinations of the mobile phase, viscosity enhancer, and excipient components listed in Table 2 were tested.

[0363] mobile phase

[0364] Suspension agents, such as glycerol, propylene glycol, PEG 200, PEG 300, and sulfolane (above their melting points or mixed with glycerol, propylene glycol, PEG 200, or PEG 300), perform well as mobile phases. Conversely, detergents such as Triton X-100, Tween 20, and Brij-type detergents, easily evaporating organic solvents such as alcohols, and water are found unsuitable as mobile phases due to problems such as foaming, loss of bead function, bead aggregation or degradation, or rapid evaporation.

[0365] Viscosity enhancer

[0366] Some PEG compounds have been successfully used as viscosity-enhancing components in formulations. Table 4 summarizes the PEG compounds found to be suitable as viscosity enhancers.

[0367] Table 4: Summary of tested viscosity enhancers.

[0368]

[0369] auxiliary materials

[0370] Solubilizers, such as urea and guanidine salts (e.g., guanidine isothiocyanate and guanidine hydrochloride), both of which are dissociative agents, and buffers, such as TAPS, HEPES, and MOPS, perform well as excipients in candidate formulations. Guanidine salts have similar effects to urea but cause beads to degrade slightly faster. Buffers, such as TAPS, HEPES, and MOPS, can be used to control pH during bead use (e.g., during DNA or RNA separation). Reagents found unsuitable for use as excipients include those listed in Table 5 below. Generally, the reagents in Table 5 cause bead stability and / or functional problems.

[0371] Table 5: Summary of reagents that are not suitable for use as pharmaceutical excipients.

[0372]

[0373] Based on the above results, a formulation was selected for further analysis. This formulation comprises a mobile phase consisting of a suspending agent (e.g., glycerol, propylene glycol, PEG 200, PEG 300, or sulfolane), a viscosity enhancer (e.g., a PEG compound such as PEG 4000, PEG 8000, PEG 10000, or PEG 20000), and a solubilizer (e.g., a liquid release agent such as urea or guanidine salt, or a buffer).

[0374] Example 2: Determining the appropriate amounts of mobile phase, viscosity enhancer, and solubilizer in a liquid formulation for storing and handling particles.

[0375] This embodiment describes experimental results for determining the appropriate proportions of a mobile phase consisting of a suspending agent (e.g., glycerol, propylene glycol, PEG 200, PEG 300, or sulfolane), a viscosity enhancer (e.g., PEG polymers such as PEG 4000, PEG 8000, PEG 10000, or PEG 20000), and a solubilizer (e.g., a dissociating agent such as urea or guanidine salt, or a buffer) in a liquid formulation intended for storing and handling particles, such as magnetic particles.

[0376] Materials and methods

[0377] Preparation of candidate formulations

[0378] To evaluate liquid formulations for storing and facilitating the handling of particles, magnetic silica beads for nucleic acid separation were used as exemplary particles, glycerol was used as an exemplary suspending agent in the mobile phase, hydrophilic polymer PEG8000 was used as an exemplary viscosity enhancer, and urea, a liquid release agent, was used as an exemplary solubilizer.

[0379] To determine the appropriate proportions of each component, candidate formulations were prepared with glycerol concentrations ranging from 70-90% (w / w), PEG 8000 concentrations ranging from 0-30% (w / w), and urea concentrations ranging from 0-30% (w / w). See Table 6.

[0380] Table 6. Candidate formulations.

[0381]

[0382] The candidate formulation was prepared according to the method described in Example 1 above, using DMSO as the organic solvent in the dehydration step (1) and the step (2) of reducing solvent content and increasing viscosity. The candidate formulation was prepared at a bead concentration of approximately 10% by weight / volume (w / v).

[0383] Evaluation of the physical properties of candidate formulations

[0384] The viscosity of candidate formulation AO (Table 6) was evaluated based on its adhesion to polypropylene surfaces, its ability to manipulate the formulation (e.g., by pipetting), and its solubility in water.

[0385] result

[0386] Table 7 shows the test results for candidate formulation AO.

[0387] Table 7: Candidate liquid formulations tested.

[0388]

[0389] Based on the results in Table 7, formulation K was selected as an exemplary formulation for further testing. Formulation K contains glycerol, PEG 8000 and urea in a ratio of 16:1:3 (i.e., 80% glycerol, 5% PEG 8000 and 15% urea, w / w).

[0390] Example 3: Characterization of a liquid formulation for enhancing storage and handling of particles.

[0391] This embodiment describes the experimental results characterizing the viscosity, density, and stability of the exemplary formulation K in Table 7 of Example 2 above.

[0392] Materials and methods

[0393] Preparation of Formulation K

[0394] Formulation K was prepared using the method described in Example 1 above, comprising glycerol, PEG 8000, and urea in a ratio of 16:1:3 (w / w) (i.e., 80% glycerol, 5% PEG 8000, and 15% urea, w / w), with DMSO used as the organic solvent in the dehydration step and in the steps of reducing solvent content and increasing viscosity. After formulation, a 5 μL volume of the formulation contained approximately 0.5 mg (±10%) of the exemplary magnetic silica beads.

[0395] Viscosity and density

[0396] The viscosity of formulation K was evaluated using a ViscoQC 300-R force viscometer equipped with a CC12 type spindle. Viscosity measurements were performed at a constant spindle speed in 5°C increments at temperatures ranging from 15°C to 60°C.

[0397] To assess density, a one-milliliter (mL) volume of the formulation was weighed on an analytical balance. Ten density measurements were repeated at approximately 22°C.

[0398] stability

[0399] The stability of the beads in formulation K was determined based on their binding to RNA after storage at room temperature (approximately 25°C) for 3, 4.5, 6, 9, 12, and 15 months. The beads were stored in a polypropylene chamber either at standard atmospheric pressure or under hypoxic conditions after the chamber was purged with nitrogen.

[0400] RNA binding was assessed as follows: RNA binding to beads In a microcentrifuge tube, mix 400 µL of eNat substrate (Copan Diagnostics, Italy), 600 µL of SA1 buffer (0.7 M sodium acetate, pH 4.9), and 500 µL of SBL buffer (75% isopropanol). Then add 3 µL of a 10% eNat solution to the tube.7 Copy (cp) / µL of the exemplary RNA target. Add 6 µL of Formulation K containing the exemplary magnetic silica beads to a microcentrifuge tube and mix. Vortex the mixture for 30 seconds, then incubate on a lab bench for 4 minutes.

[0401] Washing and elution

[0402] The beads were separated from the solution using a magnet, and then washed twice with wash buffer (10 mM glycine, pH 2.0), adding 500 µl of wash buffer each time, vortexing for 5 seconds, and then separating the beads from the wash buffer using a magnet. After the second wash, the sample was briefly centrifuged on a microcentrifuge, and then the beads were separated from the wash buffer using a magnet. As much of the wash buffer supernatant as possible was removed using a pipette. RNA was eluted from the beads by adding 100 µl of elution buffer (Tris 30 mM pH 8.8), vortexing for 15 seconds, incubating on a lab bench for 3 minutes, and then separating the particles from the eluent using a magnet. The eluent was then recovered and transferred to a new tube.

[0403] RNA recovery was analyzed by RT-qPCR.

[0404] RNA recovery was assessed using a LightCycler 480 II analyzer (Roche) via reverse transcription quantitative PCR (RT-qPCR). Three PCR replicates were prepared for each elution sample. Analysis was also performed using input RNA (in 100 µL final volume of elution buffer for 10 minutes). 7 The PCR mixtures consisted of a positive control (cp / µL), a negative control containing only elution buffer, and beads (“wet beads”) from the manufacturer’s aqueous suspension buffer. The components of the PCR mixtures are shown in Table 8.

[0405] Table 8: Master mixture for RT-qPCR reaction.

[0406]

[0407] The RT-qPCR procedure is as follows: Reverse transcription (RT): 58℃ for 30 seconds Activation: 99℃ for 2 seconds Amplification: (50x) 95℃ 1 second, 63℃ 10 seconds Melting: 65℃ for 5 seconds, 98℃ + 5℃ for 11 seconds Cooling: 37°C for 1 minute The preparation and analysis of the RT-qPCR reaction are as follows: 1. Add 9 µl of reaction mixture to the wells of the PCR plate.

[0408] 2. Add 1 µl of elution buffer, positive control (input), or negative control to the well.

[0409] 3. Seal the plate with the PCR membrane and rotate it.

[0410] 4. Run the reaction on a LightCycler 480 II analyzer (Roche).

[0411] 5. Assuming the PCR reaction efficiency is 1.9, calculate the separation efficiency using the following formula: , Where Ct 湿 It is the average cycle threshold (Ct) of the beads stored in the manufacturer's aqueous storage solution. 样品 It is the average Ct of the test sample.

[0412] result

[0413] Viscosity and density

[0414] High viscosity and density have the desired effect of preventing particles from settling in suspensions and may also contribute to particle stability, thereby facilitating the handling, dispensing and storage of particle suspensions.

[0415] The viscosity of formulation K at various ambient temperatures ranging from 15°C to 60°C is shown in Table 9.

[0416] Table 9. Viscosity of formulation K.

[0417]

[0418] The density of formulation K was determined to be approximately 1.3 g / mL (± 0.2 g / mL).

[0419] stability

[0420] The average Ct values ​​and RNA separation efficiencies of beads stored in Formulation K for 3, 4.5, 6, 9, 12, and 15 months under standard atmospheric or hypoxic conditions are shown in Table 10. Separation efficiencies are calculated relative to beads stored in the manufacturer's aqueous suspension buffer (hereinafter referred to as "wet beads").

[0421] Table 10. Ct values ​​and RNA separation efficiency at 3, 4.5, 6, 9, 12 and 15 months.

[0422]

[0423] As shown in Table 10, surprisingly, despite the relatively stringent conditions provided by Formulation K (e.g., relatively high amounts of urea), the beads stored in Formulation K remained stable and maintained their RNA-binding capacity after at least 15 months of storage under standard atmospheric and hypoxic conditions. Formulation K also unexpectedly resulted in improved RNA separation efficiency, for example, by at least approximately 10% compared to beads stored in the manufacturer's suspension buffer. See also Figure 1 Furthermore, formulation K exhibits excellent microbiological stability during prolonged storage at room temperature.

[0424] in conclusion

[0425] The results described in this embodiment demonstrate that beads stored in Formulation K are stable and functional for a surprisingly long time, for example, at least 15 months, when stored at room temperature under standard atmospheric or hypoxic conditions. Formulation K also unexpectedly leads to higher RNA isolation efficiency and exhibits excellent microbiological stability. Furthermore, Formulation K has high viscosity and density, which can facilitate bead handling and dispensing by inhibiting sedimentation and may also contribute to bead stability. Therefore, Formulation K allows for long-term storage of beads under ambient conditions while facilitating bead handling and dispensing, including through automated systems.

Claims

1. A composition comprising a plurality of particles and (a) A mobile phase containing a suspending agent; (b) Viscosity enhancers; and (c) Solubilizer.

2. The composition of claim 1, wherein: (a) The concentration of the mobile phase is between about 60% and about 99%, between about 65% and about 95%, between about 70% and about 90%, between about 75% and about 90%, or between about 80% and about 90% (w / w) by weight. (b) The suspending agent is selected from the group consisting of: sugar alcohols, glycols, water-miscible polymers, aprotic solvents, and any combination thereof; and / or (c) The mobile phase is non-aqueous or substantially non-aqueous.

3. The composition according to claim 1 or 2, wherein: (a) The viscosity enhancer is at least partially soluble in the mobile phase; (b) The concentration of the viscosity enhancer is between about 1% and about 40%, between about 1% and about 35%, between about 1% and about 30%, between about 1% and about 25%, between about 1% and about 20%, between about 1% and about 15%, between about 1% and about 10%, or between about 1% and about 5% w / w; and / or (c) The viscosity enhancer comprises a polymer that is miscible with water.

4. The composition according to any one of claims 1-3, wherein: (a) The solubilizer is at least partially soluble in the mobile phase and / or water-soluble; (b) The concentration of the solubilizer is between about 1% and about 40%, between about 5% and about 30%, between about 10% and about 25%, or between about 10% and about 20% w / w; and / or (c) The solubilizer comprises a liquid release agent or a buffer.

5. The composition of any one of claims 1-4, wherein the suspending agent comprises glycerol, the viscosity enhancer comprises PEG 8000, and the solubilizer comprises urea; optionally wherein: (i) The concentration of the glycerol is about 80% w / w, the concentration of the PEG 8000 is about 5% w / w, and the concentration of the urea is about 15% w / w, and / or (ii) The ratio of glycerol:PEG 8000:urea in the composition is 16:1:3 w / w.

6. The composition according to any one of claims 1-5, wherein: (a) When measured at room temperature, optionally at a temperature of about 25°C, the viscosity of the composition is between about 5500 mPa·s and about 7000 mPa·s, between about 5750 mPa·s and about 6750 mPa·s, or between about 6000 mPa·s and about 6500 mPa·s, optionally wherein the viscosity of the composition is evaluated using a rotational viscometer, and further optionally wherein the viscosity of the composition is evaluated at a shaft rotation speed of about 10 revolutions per minute (RPM); (b) The density of the composition is between about 0.5 g / mL and about 2 g / mL, between about 1 g / mL and about 2 g / mL, between about 1 g / mL and about 1.5 g / mL, or between about 1.1 g / mL and about 1.5 g / mL, optionally wherein the density of the composition is assessed on an analytical balance; (c) The composition is non-aqueous or substantially non-aqueous, and optionally the water content of the composition is about 1% or less; (d) Compared with corresponding particles in an aqueous solution, the composition enhances the stability of particles in a plurality of particles, wherein the particle stability is optionally assessed based on the retention of particle integrity, particle aggregation and / or ligand binding ability. (e) The plurality of particles in the composition are stable for at least about 1 month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about 12 months, at least about 13 months, at least about 14 months, or at least about 15 months, optionally wherein the particle stability is assessed based on the retention of particle integrity, particle aggregation and / or ligand binding ability; (f) The composition is able to adhere to a polypropylene surface; (g) The composition is microbiologically stable; (h) The composition further comprises a reagent selected from the group consisting of antioxidants, reducing agents, chelating agents, and any combination thereof; and / or (i) The composition does not contain antimicrobial agents and / or contains less than about 10% surfactants or detergents.

7. The composition of any one of claims 1-6, wherein the plurality of particles: (a) Contains one or more particles configured to bind nucleic acids, peptides, lipids, carbohydrates or small molecules; (b) Contains one or more microparticles, nanoparticles, microspheres, paramagnetic beads, magnetic beads, microbeads, nanobeads, or any combination thereof; (c) Contains one or more magnetic or paramagnetic particles; and / or (d) It is present in the composition at a concentration of at least about 0.5%, at least about 1%, at least about 2.5%, at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, or at least about 30% by weight / volume (w / v); or at a concentration between about 0.5% and about 30% w / v, between about 1% and about 25% w / v, between about 2.5% and about 20% w / v, or between about 5% and about 15% w / v.

8. A method for preparing a composition comprising a plurality of particles, the method comprising: (c) Provide multiple particles; and (d) Suspending the plurality of particles in a formulation containing the following substances: i. A mobile phase containing a suspending agent; ii. Viscosity enhancers; and iii. Solubilizer.

9. The method of claim 8, wherein: (1) The multiple granules provided in step (a) are dehydrated or freeze-dried; or (2) The method further includes dehydrating or freeze-drying the plurality of particles prior to step (a). Optionally, the dehydration includes suspending the plurality of particles in a first organic solvent. Further optionally, the first organic solvent comprises an organic solvent miscible with water and / or highly soluble in water, and further optionally, the first organic solvent comprises a polar aprotic solvent, a water-miscible p- or E-type glycol ether, an alcohol, tetrahydrothiophene 1-oxide, or any combination thereof.

10. The method of claim 9, wherein: (1) Step (b) includes: (i) separating a plurality of particles from a first organic solvent of a certain volume, and (ii) suspending the separated plurality of particles in a certain volume of the formulation; (2) The method further includes, prior to step (b), suspending a plurality of particles in a solution containing a second organic solvent and a suspending agent, optionally wherein step (b) comprises: (i) separating the plurality of particles from the solution containing the second organic solvent and the suspending agent, and (ii) suspending the separated plurality of particles in a volume of the formulation; and / or (3) The method further includes, prior to step (b): (i) separating a plurality of particles from a volume of a first organic solvent, and (ii) suspending the separated plurality of particles in a solution containing a second organic solvent and a suspending agent, optionally wherein step (b) includes: (i) separating the plurality of particles from the solution containing the second organic solvent and the suspending agent, and (ii) suspending the separated plurality of particles in a volume of the formulation; Choose one of them: (i) The ratio of the second organic solvent to the suspending agent in the solution is approximately 1:1; (ii) The suspending agent is selected from the group consisting of: sugar alcohols, glycols, water-miscible polymers, aprotic solvents and any combination thereof; (iii) The second organic solvent comprises an organic solvent that is miscible with water and / or has high solubility in water; and / or (iv) The second organic solvent comprises a polar aprotic solvent, a water-miscible p- or E-type glycol ether, an alcohol, or a tetrahydrothiophene 1-oxide.

11. A composition comprising a plurality of particles, said composition being produced by the method of any one of claims 8-10.

12. A method for separating an analyte from a sample, comprising: (a) Provide a sample containing the analyte; (b) The sample is mixed with a composition comprising a plurality of particles according to any one of claims 1-7 and 11 or a composition comprising a plurality of particles produced by the method according to any one of claims 8-10 to produce a mixture of the sample and the composition, thereby binding the analyte to one or more of the plurality of particles; and Optionally (c) separate multiple particles from the mixture.

13. A method for cell lysis, comprising: (a) Provide a sample containing multiple cells; (b) Mixing the sample with a composition comprising a plurality of particles as described in any one of claims 1-7 and 11, or a composition comprising a plurality of particles produced by the method as described in any one of claims 8-10, thereby producing a mixture of the sample and the composition; and (c) Stir the mixture to lyse one or more cells in the plurality of cells.

14. A kit comprising the composition of any one of claims 1-7 and 11, or a composition produced by the method of any one of claims 8-10, optionally wherein the kit further comprises: (a) Instructions for using the composition to separate one or more analytes from a sample, further optionally wherein the instructions are used for separating one or more analytes from a sample using the method according to claim 12; or (b) Instructions for using the composition to lyse one or more cells from a sample, optionally wherein the instructions are used for lysing one or more cells according to claim 13.

15. A microfluidic device comprising a composition according to any one of claims 1-7 and 11, or a liquid composition produced by the method according to any one of claims 8-10, optionally wherein the device is used to carry out the method according to claim 12 or 13.

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