A method of selectively isolating target nucleic acid molecules from a nucleic acid-containing sample, wherein the target nucleic acid molecules are within a particular molecular size range and non-target nucleic acid molecules are outside the molecular size range, comprising: contacting a sample comprising nucleic acid molecules with a matrix in the presence of a small-molecule modulator, wherein the small-molecule modulator is present in sufficient concentration that the target nucleic acid molecules selectively bind to the matrix and non-target nucleic acid molecules do not bind to the matrix and wherein increasing the concentration of the small-molecule modulator increases the molecular weight cut-off for nucleic acid molecules that bind to the matrix, and (i) wherein the small-molecule modulator is selected from diammonium phosphate, ammonium phosphate dibasic, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, monosodium phosphate, disodium phosphate, trisodium phosphate, 3-aminopropylphosphonic acid and (aminomethyl)phosphonic acid; (ii) wherein the small-molecule modulator used is of formula (Ib) wherein R 2 is a phosphate or a phosphonic acid; M is a metal or N(R a) 4; each R a is independently H or alkyl; and n is 1, 2, or 3; or a hydrate thereof; or (iii) wherein the small-molecule modulator used is a carboxylate compound of formula wherein R is selected from the group consisting of H, unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkenyl, and substituted or unsubstituted C 1 -C 8 alkynyl; M is a metal or N(R a) 4; each R a is independently H or alkyl; and n is 1, 2, or 3; or a hydrate thereof; and wherein the matrix has one or more of the following characteristics: (i) the matrix comprises silica; (ii) the matrix comprises borosilicate glass; (iii) the matrix comprises silicon dioxide-coated magnetic beads. contacting a sample comprising nucleic acid molecules with a matrix in the presence of a small-molecule modulator, wherein the small-molecule modulator is present in sufficient concentration that the target nucleic acid molecules selectively bind to the matrix and non-target nucleic acid molecules do not bind to the matrix and wherein increasing the concentration of the small-molecule modulator increases the molecular weight cut-off for nucleic acid molecules that bind to the matrix, and (i) wherein the small-molecule modulator is selected from diammonium phosphate, ammonium phosphate dibasic, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, monosodium phosphate, disodium phosphate, trisodium phosphate, 3-aminopropylphosphonic acid and (aminomethyl)phosphonic acid; (ii) wherein the small-molecule modulator used is of formula (Ib) (i) wherein the small-molecule modulator is selected from diammonium phosphate, ammonium phosphate dibasic, monopotassium phosphate, dipotassium phosphate, tripotassium phosphate, monosodium phosphate, disodium phosphate, trisodium phosphate, 3-aminopropylphosphonic acid and (aminomethyl)phosphonic acid; (ii) wherein the small-molecule modulator used is of formula (Ib) wherein R 2 is a phosphate or a phosphonic acid; M is a metal or N(R a) 4; each R a is independently H or alkyl; and n is 1, 2, or 3; or a hydrate thereof; or (iii) wherein the small-molecule modulator used is a carboxylate compound of formula (iii) wherein the small-molecule modulator used is a carboxylate compound of formula wherein R is selected from the group consisting of H, unsubstituted C 1 -C 8 alkyl, substituted or unsubstituted C 1 -C 8 alkenyl, and substituted or unsubstituted C 1 -C 8 alkynyl; M is a metal or N(R a) 4; each R a is independently H or alkyl; and n is 1, 2, or 3; or a hydrate thereof; and wherein the matrix has one or more of the following characteristics: (i) the matrix comprises silica; (ii) the matrix comprises borosilicate glass; (iii) the matrix comprises silicon dioxide-coated magnetic beads. (i) the matrix comprises silica; (ii) the matrix comprises borosilicate glass; (iii) the matrix comprises silicon dioxide-coated magnetic beads.