Carbon nanotubes combine a range of properties that make them well sui
ted for use as probe tips in applications such as atomic force microsc
opy (AFM)(1-3), Their high aspect ratio, for example, opens up the pos
sibility of probing the deep crevices(4) that occur in microelectronic
circuits, and the small effective radius of nanotube tips significant
ly improves the lateral resolution beyond what can be achieved using c
ommercial silicon tips(5). Another characteristic feature of nanotubes
is their ability to buckle elastically(4,6), which makes them very ro
bust while limiting the maximum force that is applied to delicate orga
nic and biological samples, Earlier investigations into the performanc
e of nanotubes as scanning probe microscopy tips have focused on topog
raphical imaging, but a potentially more significant issue is the ques
tion of whether nanotubes can be modified to create probes that can se
nse and manipulate matter at the molecular level(7), Here we demonstra
te that nanotube tips with the capability of chemical and biological d
iscrimination can be created with acidic functionality and by coupling
basic or hydrophobic functionalities or biomolecular probes to the ca
rboxyl groups that are present at the open tip ends. We have used thes
e modified nanotubes as AFM tips to titrate the acid and base groups,
to image patterned samples based on molecular interactions, and to mea
sure the binding force between single protein-ligand pairs. As carboxy
l groups are readily derivatized by a variety of reactions(8), the pre
paration of a wide range of functionalized nanotube tips should be pos
sible, thus creating molecular probes with potential applications in m
any areas of chemistry and biology.