Development of miniaturized devices that enable rapid and direct analysis of the specific binding of small molecules to proteins could be of substantial importance to the discovery of and screening for new drug molecules. Here, we report highly sensitive and labelfree direct electrical detection of small-molecule inhibitors of ATP binding to Abl by using silicon nanowire field-effect transistor devices. Abl, which is a protein tyrosine kinase whose constitutive activity is responsible for chronic myelogenous leukemia, was covalently linked to the surfaces of silicon nanowires within microfluidic channels to create active electrical devices. Concentration-dependent binding of ATP and concentration-dependent inhibition of ATP binding by the competitive small-molecule antagonist STI-571 (Gleevec) were assessed by monitoring the nanowire conductance. In addition, concentration-dependent inhibition of ATP binding was examined for four additional small molecules, including reported and previously unreported inhibitors. These studies demonstrate that the silicon nanowire devices can readily and rapidly distinguish the affinities of distinct smallmolecule inhibitors and, thus, could serve as a technology platform for drug discovery.inhibitors ͉ kinase ͉ Gleevec ͉ chronic myclogenous leukemia ͉ drug discovery I dentification of organic molecules that bind specifically to proteins is central to the discovery and development of new pharmaceuticals and to chemical genetic approaches for elucidating complex pathways in biological systems (1-4). Broadly representative of the importance of this concept for developing drugs to treat disease have been efforts focused on identifying inhibitors to protein tyrosine kinases (1, 5). Tyrosine kinases represent especially attractive targets because they are central elements in the networks that mediate signal transduction in mammalian cells. The regulatory function of tyrosine kinases occurs through phosphorylation of a tyrosine residue of a substrate protein by using ATP as a phosphate source (Fig. 1A) and subsequent transmission of this event through signal transduction cascade. Deregulation of phosphorylation through, for example, mutation or overexpression of protein tyrosine kinases has been linked to a number of diseases, including cancer (1, 5, 6).The identification of inhibitors to ATP or substrate protein binding thus can serve as a means of treating diseases linked to a tyrosine kinase. A successful example of this strategy has been the introduction of the small molecule STI-571, or Gleevec (Fig. 1B), which competitively inhibits ATP binding to the tyrosine kinase Abl and is a highly effective treatment for chronic myelogenous leukemia (1,5,7,8). This success and the recognition that Gleevec may be unable to cure late-stage chronic myelogenous leukemia because of mutations in the kinase (5,(8)(9)(10) suggest that the development of approaches that enable rapid, flexible, and quantitative comparison of small-molecule inhibitors of ATP or substrate protein binding to tyrosine ...

The merger of nanoscale building blocks with flexible and/or low cost substrates could enable the development of high-performance electronic and photonic devices with the potential to impact a broad spectrum of applications. Here we demonstrate that high-quality, single-crystal nanowires can be assembled onto inexpensive glass and flexible plastic substrates to create basic transistor and light-emitting diode devices. In our approach, the high-temperature synthesis of single-crystal nanowires is separated from ambient-temperature solution-based assembly to enable the fabrication of single-crystal-like devices on virtually any substrate. Silicon nanowire field-effect transistors were assembled on glass and plastic substrates and display device parameters rivaling those of single-crystal silicon and exceeding those of state-of-the-art amorphous silicon and organic transistors currently used for flexible electronics on plastic substrates. Nanowire transistor devices have been configured as low-threshold logic elements with gain; moreover, the high-performance characteristics are relatively unaffected by operation in a bent configuration or by repeated bending. The generality of this approach is further illustrated with the assembly of gallium nitride nanowire UV-light-emitting diodes on flexible plastic substrates. These results suggest that nanowires could serve as high-performance building blocks for the next of generation lightweight display, mobile computing, and information storage applications.

We investigate the self-assembly of colloidal spheres on periodically patterned templates. The surface potentials and the surface phases are induced entropically by the presence of dissolved, nonadsorbing polymers. A rich variety of two-dimensional fluidlike and solidlike phases was observed to form on template potentials with both one- and two-dimensional symmetry. The same methodology was then used to nucleate an oriented single fcc crystal more than 30 layers thick. The general approach provides a new route for directed self-assembly of novel mesoscopic structures.

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