High-Speed Mulit-Analyte Biosensor using Adaptive Laser Interferometry

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This project applies adaptive optics and laser interferometry to the sensing of bound analytes on an optical compact disk. The compact disk contains spots of antibodies (for immunological and proteomic biosensors) or complementary DNA (for genomic biosensors) arranged in concentric tracks. After exposure to a sample containing multiple analytes, the laser scans a single track at a time with sampling speeds up to one megasample per second. Bound analytes on the spinning disk modulate the phase of the reflected laser light up to a Megahertz. This phase is measured using homodyne detection in an adaptive interferometer. The key element to the interferometer is an adaptive holographic grating (a semi-insulating GaAs heterostructure) that mixes the signal (carrying the phase modulation) with a reference beam (local oscillator). The adaptive mixer is insensitive to the problems of laser speckle and mechanical vibrations that have previously prevented the use of sensitive interferometry in this application.The disk will be fabricated using soft lithography and ink-pad stamping. An important goal of the research is to study multi-analyte up-scaling from a few up to thousands of different analyzer tracks on the disk. The long-range goal of this research would be to ultimately assay almost every blood protein in a single 10 p1 sample without the need for analyte amplification.For the same reason that shot-noise-limited interferometers can detect sub-picometer surface displacements, this Biosensor CD can detect approximately 300 bound analyte molecules per spot per track. Such sensitivity can only be achieved by combining the high sampling rate of the spinning disk with the high sensitivity of adaptive interferometry. The experimental program presented here, if successful, would represent a significant improvement in the ability of biosensors to detect many low-concentration analytes.