The bottom-up assembly of functional devices requires novel building blocks to facilitate the incorporation of functional and structural hierarchy. Anisotropic building blocks can substantially broaden the creation of self-assembled devices with unique properties because of their morphological and/or chemical asymmetry. In this regard, we have created microspheres with one hemispherical face exposing silica and the other exposing gold. These microspheres were formed by the shadow deposition of gold onto silica microspheres. The two chemical surfaces allowed use of different surface reactions—silane chemistry for the silica side and thiol chemistry for the gold side—for immobilizing different oligonucleotide sequences on each of the two faces. These dual-functionalized microspheres were used in the selective orthogonal assembly of fluorophore-tagged target oligonucleotides. The DNA-directed assembly was confirmed by confocal microscopy of the microspheres. In essence, employing DNA as the linker molecule, these “Janus” particles can be assembled into various novel 1-D, 2-D, and 3-D structures, which are difficult to realize using symmetric building blocks. / Singapore-MIT Alliance (SMA)