Portable, fluorescence-based bio-molecular sensor on CMOS chip with integrated nano-optics for massively multiplexed assays

CMOS 芯片上的便携式荧光生物分子传感器，具有集成纳米光学器件，适用于大规模多重分析

• 批准号: 1610761
• 负责人: Kaushik Sengupta
• 金额: $ 36万
• 依托单位: Princeton University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1610761&HistoricalAwards=false
• 关键词: Portable; fluorescence; based; bio; molecular

Molecular diagnostics is one of the growing areas of medical diagnostics and aims to assess a person's health by detecting and measuring specific genetic sequences or proteins. Affinity-based sensing with fluorescence-based labels remains one of the most prevalent form of sensing of bio-molecules and while they are routinely used in hospitals, reference labs, and blood banks to screen for infectious diseases, current optical-based sensing technology is still complex consisting of an assembly of electronic, optical and mechanical components including lenses, objectives, collimators, multilayer thin film filters, monchrometers, photo-multiplier tubes, fiber optics, precision mechanical scanners etc., making the system large, bulky, expensive and non-portable. On the other hand, Complementary-metal-oxide-semiconductor (CMOS) technology, provides an unparalleled platform for integration of extremely complex systems, with high yield in a cost-efficient manner. The goal of the proposal is to co-opt CMOS technology and combine with new methods to integrate optical elements on the chip to realize portable, chip-scale, fluorescence-based biomolecular sensing technology. Miniaturizing an entire fluorescence sensing system from the biochemical platform to the sensor and scanner on one chip with a low-cost, optical excitation source can potentially open up completely new methodologies of in-vitro and in-vivo sensing and imaging. The ability to simultaneously sense multiple genetic as well as protein biomarkers in a rapid and multiplexed detection platform can also drastically improve the statistics of detection, critically important for diagnostics. The crosscut approach towards this project will engage and train both graduate and undergraduate students across multiple disciplines. The PI will also engage high-school seniors from local schools and broadly disseminate the knowledge through his undergraduate and graduate courses and through publications, seminars and workshops.The detection methodology for an affinity-based bio-sensor platform relies on selective target biomolecules by capturing probes and the chemistry is transduced label-free using methods such as impedance-spectroscopy, electro-analysis, Raman scattering or with magnetic, dielectric or optical labels. While detecting changes in the optical fields are mature in CMOS-based image sensors, in absence of high-performance integrated optical components, miniaturization of a fluorescence sensing system in CMOS has relied on time-resolved techniques with synchronized sources or externally grown optical filters and/or collimators which can add complexity and cost to the system. The goal of this proposal is to investigate methods by which optical field manipulation can be achieved in standard CMOS technology exploiting sub-wavelength interaction of metal-photonic nanostructures with incident optical fields in the visible range. Specifically, this work proposes design of electronic-nanophotonic architectures, signal-processing techniques and bio-interfaces on-chip with integrated 3D nanophotonic elements for massively multiplexed, fluorescence-based bio-assays. These structures are capable of excitation light suppression across a wide range of incidence angles and allow the fluorescence signal to pass, and get detected and processed over a multitude of sensor sites to enable high-density functionalized optical biosensor chips. Integrated nanoplasmonic structures in the visible range in CMOS with embedded electronics can lead to complex and miniaturized optical systems-on-chip for new applications in sensing and imaging.

分子诊断是医学诊断的增长领域之一，旨在通过检测和测量特定的遗传序列或蛋白质来评估人的健康。 Affinity-based sensing with fluorescence-based labels remains one of the most prevalent form of sensing of bio-molecules and while they are routinely used in hospitals, reference labs, and blood banks to screen for infectious diseases, current optical-based sensing technology is still complex consisting of an assembly of electronic, optical and mechanical components including lenses, objectives, collimators, multilayer thin film filters, monchrometers,照片型式管，光纤，精确的机械扫描仪等，使系统大，笨重，昂贵且不可容纳。另一方面，互补的金属氧化物 - 氧化 - 氧化物 - 氧化型技术（CMOS）技术为集成极为复杂的系统的整合提供了一个无与伦比的平台，其产量高，其产量高。该提案的目的是选择CMOS技术，并结合新方法，以整合芯片上的光学元素，以实现可移植的，基于荧光的基于荧光的生物分子传感技术。将整个荧光传感系统从生化平台到传感器到一个具有低成本，光学激发源的扫描仪的小型化，这可能会打开有关体内和体内感应和成像的全新方法论。在快速和多重检测平台中同时感知多种遗传和蛋白质生物标志物的能力也可以大大改善检测的统计数据，这对于诊断非常重要。该项目的横齿方法将跨多个学科参与并培训研究生和本科生。 PI还将吸引来自当地学校的高中生，并通过其本科和研究生课程以及通过出版物，研讨会和研讨会来广泛传播知识。基于亲和力的生物传感器平台的检测方法依赖于选择性目标生物分子的选择性探针和使用方法依赖于选择性的方法，例如，使用探针和仪式，这些方法是通过procked prockers croppy sancoppy，诸如仪式的仪式，依赖于仪式的cramepoption，这些方法是不适用的，诸如仪式均具有不合时宜的仪式。散射或磁性，介电或光学标签。在基于CMO的图像传感器中检测光场的变化是成熟的，而在没有高性能整合的光学组件的情况下，CMOS中荧光传感系统的微型化依赖于时间分辨的技术与同步源或外部成年的光过滤器和/或Complectity和Complectity和Comploce and Complectity and Comploce和成本。该提案的目的是研究在标准CMOS技术中可以实现光场操作的方法，该技术利用金属光子纳米结构的亚波长相互作用，并在可见光范围内具有入射光场。具体而言，这项工作提出了电子纳米体架构，信号处理技术和Bio Interfaces的设计，并具有集成的3D纳米元素元件，用于大量多发性，基于荧光的生物测定。这些结构能够在较大的入射角上进行激发抑制，并允许荧光信号通过，并在许多传感器位点检测和处理，以实现高密度功能化的光学生物传感器芯片。 具有嵌入式电子设备的CMO中可见范围内的可见范围内的集成纳米质结构可以导致用于感应和成像新应用的复杂和微型的光学系统。