Apparatus and methods for optical time-of-flight discrimination in combinatorial library analysis

Our recently developed method for combinatorial synthesis leads efficiently to linear arrays, where the location of a compound in the array encodes its complete synthetic history. Such arrays prepared using an optical fiber as a linear support can be probed with a fiber-guided pulse, allowing evanescent interaction with fluorescent probe molecules at the core-cladding interface. Optical time-of-flight distinction among output signals of fluorescent regions distributed along the fiber is carried out, allowing for the measurement of the location of the emitting fluorescent probes. A unique two-fiber, double-evanescent process overcomes limitations in spatial discrimination, due to fluorescence decay times in comparison to the speed of light. Investigation of an array of $102$ fluorescent regions is described, with discussion of its features and limitations.