Chiral discrimination by chemical force microscopy

Chirality is a fundamental aspect of chemical biology, and is of central importance in pharmacology, Consequently there is great interest in techniques for distinguishing between different chiral forms of a compound. Chemical force microscopy is a technique that combines chemical discrimination with atomic force microscopy by chemical derivatization of the scanning probe tip. It has been applied to the study of hydrophobic and hydrophilic interactions(1), the binding between biotin and streptavidin(2,3) and between DNA bases(4). Here we report on the use of chemical force microscopy to discriminate between chiral molecules. Using chiral molecules attached to the probe tip, we can distinguish the two enantiomers of mandelic acid arrayed on a surface, through differences in both the adhesion forces and the frictional forces measured by the probe.