Nanoplasmonics-Enhanced CMOS Fluorescence Sensors for Lens-Free Multiplexed Biomolecular Detection

用于无透镜多重生物分子检测的纳米等离子体增强型 CMOS 荧光传感器

基本信息

批准号：
1810067
负责人：
Li-Jing Cheng
金额：
$ 37.5万
依托单位：
Oregon State University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1810067&HistoricalAwards=false
关键词：
Nanoplasmonics Enhanced CMOS Fluorescence Sensors

项目摘要

Early and accurate disease diagnosis plays a decisive role in effective clinical treatment, especially at the point of care when an immediate treatment decision most needs to be made. The canonical biomarker test format for point-of-care (POC) applications is the lateral flow assay based on paper test strips which is cheap, disposable, easy to use and requires no additional hardware. However, the advantages are obtained at the expense of low sensitivity and limited quantitative measurement results. Gold standards for genetic detection and immunoassays utilize fluorescence-based detection, which offers low detection limit, high reliability, and capability of multiplexed analysis. While highly-accurate, fluorescence detection typically requires multiple optical components, making instrumentation bulky and costly for POC tests. The goal of this project is to develop a new POC testing platform that combines the benefits of high-sensitivity and quantitative analysis of fluorescence-based assays, and the simplicity, portability, and cost-effectiveness of lateral flow tests. The platform utilizes optical metamaterials-integrated photodiode array circuits to convert the enhanced fluorescence sensing signals into amplified electrical readouts to achieve sensitive detection without optical components. The lens-free design promises device miniaturization and facilitates the on-chip integration of microfluidic devices for lateral flow tests. The project fosters the development of a diverse science and engineering workforce with a deep understanding of optics at nanoscales, biosensing technology, and circuit integration. The result of the project will lead to a scalable solution that enables a sensitive, self-contained, quantitative lateral flow assay. This leverages the power and economies of scale of modern silicon integrated circuits, built up over the previous fifty years for high-performance computation and imaging, for a low-cost, bioelectronic sensing application.The key to the success of the proposed approach is to generate enhanced fluorescence and directional light emission by managing the coupling between the fluorescent reporters (fluorophores or quantum dots) on biological probes and the resonance of an optical metamaterial (Aim1). The optical metamaterials composed of metal and dielectric nanostructures exploit surface plasmons to control light. The composition of the metamaterial will be engineered to regulate the spontaneous emission rate of proximate fluorescent reporters and thus boost their emission intensity. Also, the structure of the metamaterial is designed to narrow the radiation pattern of light emission that allows guiding the light toward the photodetector for efficient optical detection. The project explores novel nanofabrication methods based on nanoparticle assembly and thin-film depositions to create large-area nanostructures for the optical metamaterials without sophisticated lithography. Monolithic integration of the metamaterial structures onto photodetector array integrated circuit (IC) substrate allows for detection of metamaterial enhanced fluorescence without optical lenses (Aim 2). A custom CMOS photodetector array IC also provides on-chip signal processing and digitization of all sensors in parallel with a simple, digital readout. A multiplexed sensor will be achieved through addressable functionalization of probe arrays on the integrated sensor substrate. Packaging of the sensor IC with microfluidic delivery using a coplanar wafer-level molding technique will result in a sensitive, miniaturized fluorescence detection platform for POC testing (Aim 3). The proposed work will elucidate the fundamentals of light-matter interactions at nanoscales, create new biosensing technologies, and design guidelines for integration of optical nanostructures, microfluidics, and CMOS ICs for a broad set of future applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

早期，准确的疾病诊断在有效的临床治疗中起决定性作用，尤其是在需要做出最多的治疗决定时。 Canonical生物标志物测试格式（POC）应用程序是基于纸质测试条的横向流量测定法，它便宜，一次性，易于使用，不需要其他硬件。但是，优势是以低灵敏度和有限的定量测量结果获得的。遗传检测和免疫测定的黄金标准使用基于荧光的检测，该检测提供了较低的检测极限，高可靠性和多重分析的能力。虽然高度准确，但荧光检测通常需要多个光学组件，使POC测试的仪器笨重且昂贵。该项目的目的是开发一个新的POC测试平台，该平台结合了基于荧光测定的高敏性和定量分析的好处，以及横向流动测试的简单性，可移植性和成本效益。该平台利用光学超材料集成的光电二极管阵列电路将增强的荧光传感信号转换为放大的电气读数，以实现无光学组件的敏感检测。无镜头设计承诺设备小型化，并促进微流体设备的片上整合以进行横向流程测试。该项目促进了多样化的科学和工程劳动力的发展，对纳米级，生物传感技术和电路整合的光学有深刻的了解。该项目的结果将导致可扩展的解决方案，以实现敏感，独立的，定量的横向流量测定法。这利用了现代硅整合电路的规模的力量和经济，在过去的五十年中建立了高性能计算和成像，以实现低成本的，生物电性的感应应用。所提出方法成功的关键是生成增强的荧光和方向光发射（通过概率的荧光量）（荧光量）（荧光量）（荧光量）（荧光量）（荧光量）（荧光量）（荧光量）（荧光量）（荧光量）（荧光量）。光学超材料的共振（AIM1）。由金属和介电纳米结构组成的光学超材料利用表面等离子体来控制光。超材料的组成将进行设计，以调节近端荧光记者的自发排放率，从而提高其发射强度。同样，超材料的结构旨在缩小光发射的辐射模式，该模式允许将光引导朝向光电探测器以进行有效的光学检测。该项目探索了基于纳米颗粒组件和薄膜沉积的新型纳米化方法，以创建用于光学超材料的大区块纳米结构，而无需复杂的光刻。超材料结构在光电探测器阵列阵列（IC）底物上的单片整合允许检测超材料增强的增强荧光，而无需光透镜（AIM 2）。自定义CMOS光电探测器阵列IC还与简单的数字读数并联提供了所有传感器的芯片信号处理和数字化。通过在集成传感器基板上对探针阵列的可寻址功能化来实现多路复用传感器。使用Coplanar晶圆级成型技术将传感器IC包装在微流体传递中，将导致一个敏感的，微型的荧光检测平台进行POC测试（AIM 3）。拟议的工作将阐明纳米级相互作用的基本面，创建新的生物传感技术，以及用于整合光学纳米结构，微流体和CMOS IC的设计指南，以弥补NSF的法定委员和范围的范围，以弥补范围的范围，以表现出众多的范围。