Melting or thermal denaturation of a DNA molecule and the different bubble-rich, premelting DNA states that serve as a precursor for DNA thermal denaturation are vital events in DNA thermophysics. In this study, we employ cantilever-based sensing to firstly pinpoint the occurrence of DNA melting and identify the temperature Tm characterizing the melting. Very importantly, this sensing is carried out with an extremely small volume (∼picoliters) of DNA sample with the cantilever demonstrating an extremely high sensitivity on the order of mJ/gK corresponding to pico-Joules of energy input. Secondly, this same large sensitivity of the cantilever is used to quantify the hitherto unknown thermophysical properties of the bubble-rich DNA premelting states. In fact, for both the melting and premelting states, the cantilever provides a framework to calculate the specific heat capacity and the storage and loss moduli of the cantilever-DNA-solution system, thereby establishing a platform for quantifying DNAs' thermo-mechanical behavior.

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