Lock-in by molecular multiplication

A lock-in amplifier is physically realized at the level of fluorescent dye molecules. It is based on the general property that the emission of a fluorescent dye is the product of quantum efficiency and illumination intensity. For each pixel of a microscopic image, we measure in amplitude and phase an environment property of the dye, such as conformation, membrane voltage, or temperature. This lock-in implementation is highly parallel and reaches the ultimate photon shot noise limit. Using fast temperature oscillations, we apply it to measure the opening/closing kinetics of a molecular beacon (DNA hairpin) at 5 mus resolution. (C) 2003 American Institute of Physics.