ABSTRACT
A reliable determination of the interaction forces requires collecting large statistical sets, which often include hundreds or thousands of individual pull-off measurements. Any potential application requiring screening of large arrays of molecules, for example, a 104 ligand library, must then collect at least 106 force curves. The high failure rate of modified AFM cantilevers observed so far in conventional CFM experiments makes this type of measurement quite challenging. Extending CFM into the realm of practical applications would require using out-of-the-box approaches. One possibility is to focus on determination of equilibrium potential energy curves, similar to the BFPR approach, which we described in the previous section. However, BFPR would typically require careful matching of the cantilever stiffness to the interaction potential, which would be difficult to adjust on-the-fly for array screening. Another possibility is to increase the throughput of the CFM measurements drastically. Pulsed force mode (PFM) measurements [99] allow to collect adhesion force data at the rates approaching 1 kHz, which is almost close to the natural limit for the adhesion measurement speed (as set by the resonance frequency of the AFM piezoelectric scanner). PFM measurements, thus, can provide high-throughput screening capability; however, they still must rely on robust cantilever functionalization.
