Resonance enhanced CMOS sensors for high-throughput sensing

项目摘要/摘要 生物分子检测微系统可在生物医学研究、临床应用中发挥重要作用 诊断、食品安全、国土安全和药物检测。这项研究的目的是 建议开发一种超灵敏、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10,000多个传感器单元，可以 提供高分辨率光谱信息，结合了免标签、高分辨率 该芯片具有高灵敏度、高吞吐量、体积小、易于与现有电子设备集成等特点。每个传感器单元 是为表面功能化的硅基高质量回音廊模式(WGM)谐振器组成的 这大约是真核细胞的大小，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。这项技术的基础是物理关联和 生物分子在微谐振器表面的相互作用可以改变光子的停留时间 通过一种新型的集成光子晶体(PC)的CMOS光谱仪进行测量和量化。此外， 提出的pc-cmos有望实现大视场(FOV)的视频帧速率光谱。 (2 cm×2 cm)和高光谱分辨率(1 Pm)。提出的传感器的独特之处在于两个方面 优势：(1)高质量WGM中显著增强的光-物质相互作用使其具有极高的灵敏度 光学微谐振器；和(2)最初采用的高通量传感机制 在半导体行业开发，用于通信和电子产品。我们的目标将是 通过完成以下三个具体目标来实现。AIM 1将在CMOS板上开发PC板条光谱仪 用于广域高分辨率光谱学的芯片。目标2将设计、制造、测量和优化 表面光栅波导管耦合的WGM微传感器阵列。目标3将演示共振增强 高分辨率的cmos光谱仪。本研究的主要创新之处有三：(1) 新的WGM传感器阵列有望提供比现有传感器高几个数量级的灵敏度 传感技术，如酶联免疫吸附试验；(2)芯片上的PC平板光谱仪，可实现单次激发 WGM微传感器10000多个光学模光谱的探测和共振增强拉曼光谱 (3)将超灵敏的WGM传感器与cmos技术相结合，实现了一个新的系统。 导致用于高灵敏度和高吞吐量的感测应用的颠覆性技术 想要。这个项目意义重大，因为这项工作的成功完成将为 新型生物传感器在临床诊断和生物医学研究中的应用 利用半导体领域的现有技术，使传统传感技术发生革命性变化 工业。如果成功，该项目开发的技术将成为美国国立卫生研究院的有力工具 以深入了解特定疾病或医疗问题为目标的R01项目。

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.