Targeted enrichment of long nucleotide sequences using microfluidic partitioning

An in vitro method for enriching one or more target DNA molecule from a sample of mixed DNA molecules comprising the steps of:

• a) providing a liquid sample of mixed DNA molecules comprising one or more specific target DNA molecule and reagents for specific detection of at least one of said target DNA molecules,
• b) forming an emulsion of a multiple of liquid droplets from said liquid sample,
• c) specifically detecting droplets containing at least one of said target DNA molecules, wherein each droplet contains less than 0.5 of said one of more target DNA molecule on average,
• d) physically selecting droplets containing at least one of said target DNA molecules, and coalescing the selected droplets, and
• e) amplifying detected DNA molecules containing at least one of said target DNA molecules in the coalesced selected droplets from step d), where the detected DNA molecules containing at least one of said target DNA molecules are in a total amount of less than 300fg, wherein general amplification reagents are added to the coalesced selected droplets to form a general amplification reaction mixture, and wherein an emulsion of droplets are formed from the reaction mixture.