Resonance enhanced CMOS sensors for high-throughput sensing

项目总结/摘要 用于检测生物分子的微系统可以在生物医学研究、临床中发挥重要作用 诊断、食品安全、国土安全和药物检测。本研究的目的是 建议是开发一种超灵敏和高通量的互补金属氧化物， 半导体（CMOS）传感器，其包括在1英寸芯片上的超过10，000个传感器单元， 提供了高分辨率的光谱信息，具有无标记，高分辨率， 灵敏度、高通量、小尺寸和易于与现有电子器件集成。每个传感器单元 用于表面功能化的基于二氧化硅的高质量回音壁模式（WGM）谐振器 其大小接近真核细胞，用于对特定蛋白质进行超灵敏的无标记生物传感， 生物标志物和蛋白质-蛋白质相互作用。该技术的基础是物理关联， 微谐振器表面上的生物分子的相互作用改变光子的停留时间， 测量和量化的一种新的光子晶体（PC）集成CMOS光谱仪。而且 提出的PC-CMOS有望实现具有大视场（FOV）的光谱学的视频帧速率 （2 cm × 2 cm）和高光谱分辨率（1 pm）。所提出的传感器的独特之处在于两个 优点：（1）高质量WGM中显著增强的光-物质相互作用使超灵敏度成为可能 光学微谐振器;（2）最初采用CMOS的高通量传感机制 在通信和电子产品半导体行业中开发。我们的目标是 实现以下三个具体目标。目标1将在CMOS上开发PC板光谱仪 用于宽视场高分辨率光谱分析的芯片。目标2将设计，制造，测量和优化 表面光栅波导耦合WGM微传感器阵列。目标3将展示共振增强 高分辨率CMOS光谱仪本研究的创新点主要有三点：（1） 新型WGM传感器阵列有望提供比现有传感器阵列高几个数量级的灵敏度 传感技术，如ELISA;（2）在CMOS芯片上的PC板光谱仪，它可以实现单次拍摄 检测WGM微传感器和共振增强拉曼的10，000多个光学模式光谱 （3）将超灵敏WGM传感器与CMOS技术集成，以实现新的系统 从而导致用于其中高灵敏度和高吞吐量 需要的话这一项目意义重大，因为这项工作的成功完成将为 开发一种具有巨大潜力的新型生物传感器，以推进临床诊断和生物医学研究， 通过利用半导体领域的现有技术， 行业如果成功，该项目开发的技术将能够作为NIH的强大工具， R 01项目旨在深入了解特定疾病或医疗问题。

PROJECT SUMMARY/ABSTRACT Microsystems for the detection of biomolecules can play important roles in biomedical research, clinical diagnosis, food safety, homeland security and pharmaceutical testing. The research objective of this proposal is to develop an ultrasensitive and high-throughput complementary metal–oxide– semiconductor (CMOS) sensors including over 10,000 sensor units on a 1-inch chip that could provided high-resolution spectroscopic information with combined features of label-free, high sensitivity, high throughput, small size, and easy integration with existing electronics. Each sensor unit is composed for surface-functionalized silica-based high-quality whispering-gallery-mode (WGM) resonators that approximate the size of eukaryotic cells for ultra-sensitive label-free biosensing of specific proteins, biomarkers and protein-protein interactions. The basis for the technology is the physical associations and interactions of biomolecules on a microresonator surface alter the residence time of photons in a way that can be measured and quantified by a novel photonic crystal (PC) integrated CMOS spectrometer. Moreover, the proposed PC-CMOS is expected to achieve a video-frame rate of spectroscopy with a large field of view (FOV) (2 cm × 2 cm) and high spectral resolution (1 pm). The unique features of the proposed sensor lie in two advantages: (1) ultrasensitivity enabled by significantly enhanced light-matter interactions in high-quality WGM optical microresonators; and (2) high-throughput sensing mechanisms adopted from CMOS originally developed in the semiconductor industry for communications and electronic products. Our objective will be achieved by completing the following three specific aims. Aim 1 will develop PC slab spectrometer on a CMOS chip for wide-field high-resolution spectroscopy. Aim 2 will design, fabricate, measure, and optimize the surface-grating-waveguide-coupled WGM microsensor arrays. Aim 3 will demonstrate resonance-enhanced high-resolution CMOS spectrometer. The proposed research contains three main innovations: (1) the novel WGM sensor arrays are expected to offer several orders of magnitude higher sensitivity than existing sensing technologies, such as ELISA; (2) PC slab spectrometer on a CMOS chip, which enables a single-shot detection of over 10,000 optical mode spectra of the WGM microsensors and resonance-enhanced Raman spectroscopy; (3) integrating ultrasensitive WGM sensors with CMOS technologies to realize a new system leading to a disruptive technology for sensing applications where high sensitivity and high throughput are desired. This project is significant because successful completion of this work will lay the foundation for the development of a new biosensor with great potential to advance clinical diagnosis and biomedical research by revolutionizing conventional sensing technologies by leveraging the existing technologies in semiconductor industries. If successful, the technology developed in this project will be able to serve as a powerful tool for NIH R01 projects targeting for an in-depth understanding of specific diseases or medical problems.