A method of enriching a variant of a target nucleic acid sequence in a mixture of nucleic acids from a sample, the target nucleic acid existing in the form of two variant sequences, wherein said variants differ at a single nucleotide position, the method comprising: providing the sample that includes the target nucleic acid sequence wherein the variant to be enriched is present in the sample in low abundance amongst a large excess of the other variant; providing an oligonucleotide that is complementary to one strand of the target nucleic acid sequence, wherein the oligonucleotide has a mismatch at the single nucleotide position with the variant to be enriched and is perfectly matched at the single nucleotide position with the other variant; heating the sample such that the mixture of nucleic acid is denatured providing conditions suitable for hybridization of the oligonucleotide to the target nucleic acid to generate duplex polynucleotides consisting of the oligonucleotide and one strand of either variant of the target nucleic acid sequence; heating the sample such that the mixture of nucleic acid is denatured; contacting the duplex polynucleotides with a mismatch intercalating compound that is attached with an affinity label to generate a reaction mixture, wherein said mismatch intercalating compound is capable of binding to the duplex polynucleotides that contain a mismatch and is not capable of binding to the duplex polynucleotides that do not contain a mismatch; subjecting the reaction mixture to an affinity matrix that recognizes and binds to the affinity label on the mismatch intercalating compound; washing the reaction mixture and separating the affinity matrix from all material that is not bound to the affinity matrix; and providing a buffer to elute nucleic acid from the affinity matrix, and collecting the eluted buffer which contains the enriched variant of the target nucleic acid sequence, wherein the mismatch intercalating compound with the affinity label is Rh(bpy) 2 (phzi)(PEG3-Biotin) 3+ present at a concentration above 15μM. providing the sample that includes the target nucleic acid sequence wherein the variant to be enriched is present in the sample in low abundance amongst a large excess of the other variant; providing an oligonucleotide that is complementary to one strand of the target nucleic acid sequence, wherein the oligonucleotide has a mismatch at the single nucleotide position with the variant to be enriched and is perfectly matched at the single nucleotide position with the other variant; heating the sample such that the mixture of nucleic acid is denatured providing conditions suitable for hybridization of the oligonucleotide to the target nucleic acid to generate duplex polynucleotides consisting of the oligonucleotide and one strand of either variant of the target nucleic acid sequence; heating the sample such that the mixture of nucleic acid is denatured; contacting the duplex polynucleotides with a mismatch intercalating compound that is attached with an affinity label to generate a reaction mixture, wherein said mismatch intercalating compound is capable of binding to the duplex polynucleotides that contain a mismatch and is not capable of binding to the duplex polynucleotides that do not contain a mismatch; subjecting the reaction mixture to an affinity matrix that recognizes and binds to the affinity label on the mismatch intercalating compound; washing the reaction mixture and separating the affinity matrix from all material that is not bound to the affinity matrix; and providing a buffer to elute nucleic acid from the affinity matrix, and collecting the eluted buffer which contains the enriched variant of the target nucleic acid sequence, wherein the mismatch intercalating compound with the affinity label is Rh(bpy) 2 (phzi)(PEG3-Biotin) 3+ present at a concentration above 15μM.