Credit: © 2007 ACS

In 'inverted' atomic force microscopy (AFM), the sample of interest is attached to the end of a tipless cantilever, which is then probed with a microfabricated array of tips on a surface. This design allows the screening of large combinations of interactions because different chemical 'libraries' can be put on the tipless cantilever and the tip arrays — a technique know as combinatorial AFM. Modifying the cantilever with different chemistries using conventional patterning methods, however, has been limited by the need for expensive instruments.

Researchers at the University of Alberta in Canada now report a simple way to pattern the cantilever and measure combinations of interactions with an array of chemically modified tips. John-Bruce Green and colleagues1 coated gold nanorods with different thiol molecules and manually deposited them on a tipless cantilever. A substrate-supported array of four gold-coated tips was then manually spotted to coat each tip with another four different chemical groups. Using this inverted AFM set up, they measured the 16 different tip–rod interactions and generated force curves. Because each of the chemical groups on the tip and rod interacted with a different adhesion force, their identities could be determined from the curves.

Although there is still plenty of room for improvement, this work highlights the potential of using combinatorial AFM to interrogate chemical libraries in a high-throughput fashion.