Systems and methods for enhanced SCODA

A method of separating differentially methylated nucleic acid molecules, comprising:

• providing first and second nucleic acid molecules, the first and second nucleic acids molecules being at least 95% identical in sequence but being differentially methylated,
• contacting a matrix comprising an oligonucleotide probe with the first and second nucleic acids, wherein the difference between the melting temperature of the first nucleic acid molecule complexed with the oligonucleotide probe and the melting temperature of the second nucleic acid molecule complexed with the oligonucleotide probe is less than about 10° C.;
• and
• applying a time-varying electric field to the matrix while synchronously varying the mobility of the first and second nucleic acids, thereby separating the first and second nucleic acid molecules.

A method of separating differentially methylated nucleic acid molecules, comprising:

• providing first and second nucleic acid molecules, the first nucleic acid molecule and the second nucleic acid molecule are methylated at different nucleotides;
• contacting a matrix comprising an oligonucleotide probe with the first and second nucleic acids;
• and
• applying a time-varying electric field to the matrix while synchronously varying the mobility of the first and second nucleic acids, thereby separating the first and second nucleic acid molecules.

A method of separating differentially methylated nucleic acid molecules, comprising:

• providing first and second nucleic acid molecules, the first and second nucleic acids molecules being at least 95% identical in sequence but being differentially methylated;
• contacting a matrix comprising a plurality of different oligonucleotide probes with the first and second nucleic acids;
• and
• applying a time-varying electric field to the matrix while synchronously varying the mobility of the first and second nucleic acids, thereby separating the first and second nucleic acid molecules.