Combinatorial techniques to synthesize a host of new compounds are being rapidly developed, leading to new candidates for therapeutic and diagnostic treatments. In contrast, the development of techniques to exploit these combinatorial libraries has been relatively static. In every method the recognition step relies on strong adsorption of the antigen of interest to one member of the library. This recognition step could overlook moderate interactions or subtle differences that could provide important clues for further screening. In addition, this step limits the use of mixed libraries in screening protocols. They propose to develop a new recognition step that will circumvent the above difficulties. The method is applicable to combinatorial libraries on smooth, flat surfaces. The method involves the direct measurement of the interaction of the antigen with each library member using atomic force microscopy. If successful, the proposed method would provide a quantitative measure of the interaction of each library member with an antigen of interest. This would be a new technique to characterize antigens. The method would also enhance the use of mixed libraries in screening protocols. This could result in highly efficient screening protocols that require a lower number of library members.
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