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基于硅基光子集成电路芯片的单分子检测技术

Single-Molecule Detection by Silicon-based Photonic Integrated Circuits Chip

  • 摘要: 单分子检测技术作为解析生命活动分子机制与基础物理化学过程的核心工具,在跨尺度科学研究中发挥着非常重要的作用. 得益于卓越的灵敏度和极低的样本需求,近年来,单分子检测技术在医学诊断中的应用引起越来越多的关注. 然而,以全内反射荧光显微镜为代表的经典单分子检测技术,受限于复杂的光路校准流程、严苛的倏逝场激发条件和有限的并行检测能力,难以实现临床诊断的大规模应用与推广. 针对上述技术瓶颈,本文开发了一种基于硅基光子集成芯片的单分子荧光检测创新方案,为低成本、易操作的单分子检测方案提供了新选择. 通过使用一些基础的光学元件,利用高折射率波导的强倏逝场作为单分子荧光的激发光源,使用包括水浸物镜、中继光学系统和数字相机在内的简单光学系统作为荧光信号的收集系统. 研究结果表明,基于集成硅光子芯片的单分子检测技术在成本、通量和操作便捷性方面具有明显优势,有望推动单分子荧光检测在医学诊断中的广泛应用.

     

    Abstract: The single-molecule detection technique plays a pivotal role in elucidating the fundamental mechanisms of various scientific processes at the molecular level, and holds essential importance in multiple fields including physics, biology, and chemistry. Recently, single-molecule detection has garnered increasing attention owing to its practical utility in medical diagnosis, primarily due to its exceptional sensitivity and the minimal sample volume required for analysis. However, the conventional single-molecule technique, represented by total internal reflection microscopy, faces challenges such as sophisticated operation procedures and limited detection throughput, thereby impeding its broader application. To address these limitations, we have demonstrated single-molecule detection using an integrated silicon photonic chip, offering a cost-effective and user-friendly alternative. By employing basic optics, we efficiently introduce the excitation source for single-molecule fluorescence by harnessing the strong evanescent field of high refractive-index waveguides. Subsequently, fluorescence signals are collected using basic optics comprising a water-immersion objective, relay optics, and a digital camera. Our results highlight a low-cost, high-throughput single-molecule technique achieved through the integrated silicon photonic chip. This innovative approach is promised to facilitate the widespread adoption of single-molecule fluorescence in medical diagnosis.

     

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