The adaptive BioCD: Interferometric immunoassay on a spinning disk

The speed of interferometric detection is at least 1000 times faster than the fluorometric detection used in the vast majority of clinical diagnostic systems. This opens the possibility to perform thousands of assays in the time it takes fluorescence to perform only one. Molecules immobilized on a spinning disk, like a CD, present the fastest and simplest means of interrogating thousands of micron-scale interferometer elements per second. However, the challenge of interferometry on a spinning disk is to maintain stable phase in the presence of mechanical vibration. In this paper, we demonstrate the first use of adaptive optics in an adaptive optical homodyne mixer to perform interferometry on a multi-analyte BioCD. The BioCD is a 4, diameter glass disk printed with a spoke pattern of protein. When the disk spins, the periodic protein pattern is transferred into a high-speed optical phase modulation by spinning the disk at 3000 rpm in the path of a probe laser. A nonlinear optical film mixes the signal beam with a stable reference beam in a two-wave mixing configuration that adaptively phase-locks the two beams to create stable phase in spite of mechanical vibration. Specific binding of antibody to printed antigen is detected as an increased homodyne signal. Multi-analyte detection on Anti Mouse and Anti Rabbit IgG is performed in which Mouse IgG and Rabbit IgG act as the non-specific reagent to each other. Detection is made on circular tracks. The technique has the potential of fast screening for large numbers of protein interactions.