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Optical Biosensor based on Silicon-on-Insulator Microring Cavities for Specific Protein Binding Detection

机译:基于绝缘体上硅微环腔的光学生物传感器用于特异性蛋白质结合检测

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Label-free biosensors for protein detection try to overcome the stability and reliability problems of commercialized systems relying on the detection of labeled molecules. We propose a micron sized integrated Silicon-on-Insulator optical biosensor based on a microring cavity that enables real time and sensitive measurements of protein dynamics, fast sample preparation and multiparameter detection for extremely low analyte quantities. Fabrication with Deep UV lithography for standard CMOS processing allows for cheap mass production and integration with electronic functions for complete lab-on-chip devices. The SOI material system offers a high refractive index contrast suitable for the fabrication of submicron sized optical cavities of very high quality. The shift of resonance wavelength that occurs when the dielectric surroundings of such a cavity is changed, is used for sensing. We demonstrate a SOI optical microring resonator with radius 5 micron capable of detecting bulk refractive index changes of 10~(-4). Modification of the semiconductor surface, allowing for immobilization of biomolecules, is characterized by X-ray Photoelectron Spectroscopy, ellipsometry, Scanning Contact Angle and Atomic Force Microscopy. We use the avidin/biotin high affinity couple to demonstrate good repeatability and the detection of protein concentrations down to 50 ng/ml. Negative control using low interaction protein couples shows low responses, proving the realization of real specific binding. Integration with a microfluidic setup will allow for more precise monitoring of the interaction dynamics, while lining up the microrings in arrays will allow for cheap high throughput label-free multiparameter analyses.
机译:用于蛋白质检测的无标记生物传感器试图克服依赖于标记分子检测的商业化系统的稳定性和可靠性问题。我们提出了一种基于微环腔的微米级绝缘体上集成硅光学生物传感器,该传感器能够实时,灵敏地测量蛋白质动力学,快速制备样品并进行多参数检测,以实现极低的分析物量。利用用于标准CMOS处理的深紫外光刻技术,可以进行廉价的批量生产,并与完整的片上实验室设备的电子功能集成在一起。 SOI材料系统提供了高折射率对比,适用于制造质量非常高的亚微米尺寸的光腔。当这种空腔的电介质周围环境发生变化时发生的谐振波长偏移用于感应。我们证明了半径为5微米的SOI光学微环谐振器能够检测10〜(-4)的整体折射率变化。通过X射线光电子能谱,椭圆偏振,扫描接触角和原子力显微镜,可以对半导体表面进行修饰,从而实现生物分子的固定化。我们使用抗生物素蛋白/生物素高亲和力对来证明良好的重复性和检测低至50 ng / ml的蛋白质浓度。使用低相互作用蛋白对的阴性对照显示低响应,证明实现了真正的特异性结合。与微流控装置集成将允许更精确地监测相互作用动力学,而将微环排列成阵列将允许进行廉价的高通量无标签多参数分析。

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