High-Speed Mulit-Analyte Biosensor using Adaptive Laser Interferometry

本计画应用自适应光学与雷射干涉测量法于光学光碟上结合分析物的感测。光盘包含抗体点（用于免疫学和蛋白质组学生物传感器）或互补DNA（用于基因组生物传感器），排列在同心轨道上。在暴露于含有多种分析物的样品后，激光每次扫描一个轨道，采样速度高达每秒一百万个样品。旋转圆盘上的结合分析物将反射激光的相位调制到兆赫。该相位使用自适应干涉仪中的零差检测来测量。干涉仪的关键元件是自适应全息光栅（半绝缘GaAs异质结构），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，这些问题以前妨碍了在该应用中使用灵敏的干涉测量法。该研究的一个重要目标是研究多分析物放大，从磁盘上的几个到数千个不同的分析仪轨道。这项研究的长期目标是最终在一个10 p1的样本中检测几乎所有的血液蛋白质，而不需要分析物扩增。出于与散粒噪声限制干涉仪可以检测亚皮米表面位移相同的原因，该生物传感器CD可以检测每个斑点每个轨道大约300个结合的分析物分子。这种灵敏度只能通过将旋转盘的高采样率与自适应干涉测量的高灵敏度相结合来实现。这里提出的实验方案，如果成功的话，将代表生物传感器检测许多低浓度分析物的能力的显着提高。

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.