Research at the forefront of chemistry and biology aims to understand the energetics and dynamics of complex single molecules such as DNA, RNA, and proteins. Our approach is to use OT to “grab” colloidal beads that we attach to the ends of a single DNA molecule and to stretch the spaghetti-like molecule while measuring the energy required to effect tension-induced transitions. Our aim is to apply the OT technique to biophysical systems (i) to quantify the energy of specific protein/DNA interactions that are important to chromosomal replications, and (ii) to quantify the energy of local denaturation, or “melting” of dsDNA, an important first step in the biochemistry of DNA and RNA. The single molecule experiments are analogous to conventional calorimetry measurements that detail the energetics of an ensemble or collection of molecules.