Recent work has demonstrated the ability to measure forces between and within single molecules using cantilever-based instruments. Force measurements on molecules can provide structural and dynamic information not available with other techniques. Figure 1 shows an example force-distance curve made of lambda digest DNA being stretched by a cantilever, showing the characteristic plateau at 65 pN as the DNA goes through the B-S transition. Implicit in these measurements is a need for carefully quantifying the forces the cantilever is exerting on the single molecule. This requires a low noise system that provides accurate measurements of the cantilever spring constant, cantilever bending, and the relative cantilever-sample separation. We have developed an instrument with several improvements that allows these measurements to be made quantitatively. One component is an improved optical lever that provides an extremely sensitive measurement of the cantilever deflection. A separate sensor measures the position of the moving base of the cantilever and allows thermal drift, piezo scanner hysteresis, and creep effects to be corrected.

In force measurements with micro-machined cantilevers the application of Hooke's law (F = −kx) requires two quantities: x, the distance the flexing cantilever moves and the “spring constant” k. The optical lever is the most commonly used method for measuring the deflection of a cantilever.