Resonance enhanced CMOS sensors for high-throughput sensing

用于高通量传感的共振增强型 CMOS 传感器

• 批准号: 10303973
• 负责人: Lan Yang
• 金额: $ 28.85万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10303973
• 关键词: Achievement; Address; Adopted; Algorithms; Binding; Biochemical; Biomedical Research; Biosensing Techniques; Biosensor; Communication; Coupled; Crystallization; Detection; Development; Diagnostic; Disease; Electronics; Enzyme-Linked Immunosorbent Assay; Eukaryotic Cell; Food Safety; Foundations; Individual; Industry; Label; Light; Measures; Medical; Medical Research; Medicine; Methods; Optics; Pharmacologic Substance; Photons; Play; Public Health; Pump; Raman Spectrum Analysis; Refractive Indices; Research; Resolution; Role; Security; Semiconductors; Signal Transduction; Silicon Dioxide; Spectrum Analysis; Structure; Surface; System; Techniques; Technology; Testing; Time; United States National Institutes of Health; Work; base; clinical Diagnosis; clinical application; cost; design; detection sensitivity; disease diagnosis; improved; innovation; light intensity; metal oxide; microsensor; microsystems; nanophotonic; novel; photonics; protein biomarkers; protein protein interaction; reconstruction; residence; sensor; sensor technology; single molecule; tool

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.

项目概要/摘要 用于检测生物分子的微系统可以在生物医学研究、临床研究中发挥重要作用 诊断、食品安全、国土安全和药物测试。本次研究的目的 建议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，在 1 英寸芯片上包含超过 10,000 个传感器单元， 提供高分辨率光谱信息，具有无标记、高 灵敏度高、吞吐量高、尺寸小且易于与现有电子设备集成。每个传感器单元 专为表面功能化二氧化硅基高质量回音壁模式 (WGM) 谐振器而设计 近似真核细胞的大小，用于特定蛋白质的超灵敏无标记生物传感， 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和 微谐振器表面上生物分子的相互作用改变光子的停留时间，从而可以 通过新型光子晶体 (PC) 集成 CMOS 光谱仪进行测量和量化。此外， 所提出的 PC-CMOS 有望实现大视场 (FOV) 光谱的视频帧率 (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) 通过显着增强高质量 WGM 中的光与物质相互作用实现超灵敏 光学微谐振器； (2) 最初采用CMOS的高通量传感机制 为通信和电子产品的半导体行业而开发。我们的目标是 通过完成以下三个具体目标来实现。目标 1 将开发 CMOS 上的 PC 平板光谱仪 宽视场高分辨率光谱芯片。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。本研究包含三个主要创新点：（1） 新型 WGM 传感器阵列预计将提供比现有传感器高几个数量级的灵敏度 传感技术，例如 ELISA； (2) CMOS 芯片上的 PC 平板光谱仪，可实现单次 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 光谱学； (3)将超灵敏WGM传感器与CMOS技术集成以实现新系统 为高灵敏度和高吞吐量的传感应用带来颠覆性技术 想要的。该项目意义重大，因为这项工作的成功完成将为下一步的发展奠定基础。 开发一种新型生物传感器，具有推进临床诊断和生物医学研究的巨大潜力 利用半导体现有技术彻底改变传统传感技术 行业。如果成功，该项目开发的技术将能够成为 NIH 的强大工具 R01项目旨在深入了解特定疾病或医疗问题。