New Approaches to the Synthesis of Addressable Microarray Molecular Libraries
Approaches for the synthesis of molecular libraries on addressable arrays of microelectrodes are presented. In each case, substrates are fixed to a polymer coating of the array in the regions proximal to the microelectrodes. Selected micro-electrodes are then used to synthesize chemical reagents that initiate reactions involving the substrates. The reagents generated at the electrodes are confined to the region of the array next to the selected electrodes by placing a second substrate that consumes the reagent in the reaction solution above the array. In addition, a strategy for characterizing the molecules synthesized in this manner, and a strategy for probing their biological activity are described.
KeywordsReductive Amination Heck Reaction Microelectrode Array Fmoc Group Ethyl Vinyl Ether
We thank the National Science Foundation (CHE-0314057; CHE-0518063) and CombiMatrix for their generous support of this work. We also gratefully acknowledge the Washington University High Resolution NMR facility, partially supported by NIH grants RR02004, RR05018, and RR07155, and the Washington University Mass Spectrometry Resource Center, partially supported by NIHRR00954, for their assistance. Professor Amy Walker of Washington University is gratefully acknowledged for her collaboration on the TOF-SIMS work, as is Kris Roth for his collaboration in connection with the signaling portion of this work. Finally, we wish to acknowledge the students (Dr. Eden Tesfu, Dr. Jun Tian, Ms. Ceng Chen, and Ms. Gabriella Nagy) without whom none of this work would be accomplished.