Circular-difference response of second-harmonic generation from chiral
surfaces is shown to be a sensitive probe of chiral biological sample
s. The sensitivity of this nonlinear effect is several orders of magni
tude higher than that of linear circular dichroism and is demonstrated
using samples of bacteriorhodopsin. This nonlinear optical activity p
robes molecular chirality on a more general level than linear techniqu
es. Surface specifity of the novel approach can be of considerable imp
ortance in the study of biological membranes. Hence, this process has
the potential of becoming a new chiro-optical tool in the fields of an
alytical (bio)chemistry, surface chemistry, and cell biology.