Fast Detection of Biomolecules in Diffusion-Limited Regime Using Micromechanical Pillars

We have developed a micromechanical sensor based on vertically oriented oscillating beams, in which contrary to what is normally done (for example with oscillating cantilevers) the sensitive area is located at the free end of the oscillator. In the micropillar geometry used here, analyte adsorption is confined only to the tip of the micropillar, thus reducing the volume from which the analyte molecules must diffuse to saturate the surface to a sphere of radius more than 2 orders of magnitude smaller than the corresponding linear distance valid for adsorption on a macroscopic surface. Hence the absorption rate is 3 orders of magnitude faster than on a typical 200 × 20 square micrometer cantilever. Pillar oscillations are detected by means of an optical lever method, but the geometry is suitable for multiplexing with compact integrated detection. We demonstrate our technology by investigating the formation of a single-strand DNA self-assembled monolayer (SAM) consisting of less than 10(6) DNA molecules and by measuring their hybridization efficiency. We show that the binding rate is 1000 times faster than on a "macroscopic" surface. We also show that the hybridization of a SAM of maximum density DNA is 40% or 4 times the value reported in the literature. These results suggest that the lower values previously reported in the literature can be attributed to incomplete saturation of the surface due to the slower adsorption rate on the "macroscopic" surfaces used.