Distinguishing the target DNA from its single-base altered counterpart provides valuable information for disease diagnosis,personalized medicine,and basic biochemical research.High resolution melting (HRM) is a newly developed post-PCR (polymerase chain reaction) analysis method for identifying genetic variations.It employs fluorescence from intercalating dyes to differentiate the melting curve of two DNA sequences.However,fluorescence difference between the target and mismatched DNA generally become indistinguishable with the increased sequence length.We propose to develop a highly specific intra-cavity DNA detection scheme using an optofluidic laser that is capable of analyzing DNA sequences of hundreds to thousands of bases long.DNA samples and fluorophores are incorporated as part of the laser gain medium.Stimulated laser emission,rather than fluorescence (i.e.,spontaneous emission),is employed as the sensing signal.As compared to the conventional HRM,the proposed intra-cavity analysis has a number of distinct advantages.(1) For a given fluorophore quantity,the laser emission is usually 103-104 stronger than fluorescence,making the system noise comparatively small or even negligible; (2) More importantly,due to the strong optical feedback provided by the laser cavity,the small difference in the laser gain caused by the small yet intrinsic thermal dynamic difference between the target and the single-base mismatched DNA will be significantly amplified.Consequently,a differential signal as large as 104-105 can potentially be achieved,even with DNA of thousands of bases long; (3) When temperature increases,the laser undergoes an extremely sharp phase transition from stimulated emission to fluorescence,which allows us to precisely determine the melting temperature difference of two DNA sequences; (4) The optofluidic laser is highly compatible with on-chip droplet-based PCR and microfluidic configurations,and requires only nano-liter sized sample volumes.