High-Speed Mulit-Analyte Biosensor using Adaptive Laser Interferometry

该项目将自适应光学和激光干涉术应用于检测光盘上的结合分析物。光盘包含以同心轨迹排列的抗体(用于免疫和蛋白质组生物传感器)或互补DNA(用于基因组生物传感器)的斑点。在暴露于含有多个分析物的样本后，激光一次扫描一条轨道，采样速度高达每秒一兆样本。旋转圆盘上的结合分析物将反射激光的相位调制到兆赫。在自适应干涉仪中使用零差检测来测量该相位。干涉仪的关键元件是自适应全息光栅(一种半绝缘的砷化镓异质结)，它将信号(携带相位调制)与参考光束(本地振荡器)混合。自适应混合器对激光散斑和机械振动问题不敏感，这些问题以前阻碍了敏感干涉测量在这一应用中的使用。光盘将使用软光刻和墨垫冲压制造。这项研究的一个重要目标是研究多分析物在磁盘上从几个到数千个不同的分析器轨道的放大。这项研究的长期目标是最终在不需要分析物放大的情况下分析单个10p1样本中的几乎每一种血液蛋白。由于散粒噪声受限的干涉仪可以检测亚皮米表面位移的相同原因，这种生物传感器CD可以在每个轨迹的每个点检测大约300个结合的分析物分子。只有将旋转圆盘的高采样率与自适应干涉测量的高灵敏度结合起来，才能实现这种灵敏度。这里提出的实验计划，如果成功，将代表着生物传感器检测许多低浓度分析物的能力的显著改进。

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.