Microelectrode Arrays: Moving Toward the Synthesis of More Complex Surfaces

Microelectrode arrays can be ideal tools for probing a host of biological interactions. Yet in spite of their general utility, their use is still limited by our ability to construct complex molecular surfaces that can spatially isolate molecules in specific locations proximal to specific electrodes. With this in mind, we have been developing electrochemically based tools that allow for the placement of molecules by specific electrodes in an array and then probe the binding of those molecules with biological targets in “real-time”. Yet while those methods are very useful, they have limits. They enable the analysis of smaller libraries, but are not as effective if one wants to probe a receptor with even a medium size library. The problem is that the tools developed to date require a library to be synthesized at a remote site and then transfer that library to the array one molecule at a time. For larger libraries, this is time consuming and cumbersome. A better strategy would be to build the library directly on the array. The approach to building a molecular library typically involves a diversification strategy like the one shown in Scheme 1. In the Scheme, P1-P4 represent protecting groups that can be orthogonally removed. But what are the orthogonal protecting groups that can be removed site-selectively on a microelectrode array so that such a strategy can be used to synthesize more complex molecular surfaces? Furthermore, are the current surfaces used on the arrays compatible with such an intensive synthetic effort? In the talk to be given, we will describe initial findings that begin to address these questions as we push for the development of new methods that will allow for the greater community to take full advantage of what microelectrode arrays can offer. Figure 1