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对于有效的临床治疗起着决定性作用，特别是在最需要立即做出治疗决定的护理点。用于现场护理 (POC) 应用的标准生物标志物测试格式是基于纸质测试条的侧向层析检测，该检测价格便宜、一次性、易于使用且不需要额外的硬件。然而，这些优势是以低灵敏度和有限的定量测量结果为代价获得的。基因检测和免疫分析的黄金标准采用基于荧光的检测，其检测限低、可靠性高且具有多重分析能力。虽然荧光检测精度很高，但通常需要多个光学元件，这使得 POC 测试仪器体积庞大且成本高昂。该项目的目标是开发一种新的 POC 测试平台，该平台结合了基于荧光的检测的高灵敏度和定量分析的优点，以及侧流测试的简单性、便携性和成本效益。该平台利用光学超材料集成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读数，从而无需光学元件即可实现灵敏检测。无透镜设计有望实现设备小型化，并促进用于侧流测试的微流体设备的片上集成。该项目促进了对纳米级光学、生物传感技术和电路集成有深入了解的多元化科学和工程队伍的发展。该项目的成果将产生一个可扩展的解决方案，实现灵敏、独立、定量的侧流检测。这利用了现代硅集成电路的功率和规模经济，这些集成电路是在过去五十年中为高性能计算和成像而建立的，用于低成本的生物电子传感应用。所提出的方法成功的关键是通过管理生物探针上的荧光报告基团（荧光团或量子点）与光学超材料（Aim1）的共振之间的耦合，产生增强的荧光和定向光发射。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。超材料的成分将被设计为调节邻近荧光报告基因的自发发射率，从而提高其发射强度。此外，超材料的结构被设计为缩小光发射的辐射图案，从而允许将光引导至光电探测器以进行有效的光学探测。该项目探索基于纳米颗粒组装和薄膜沉积的新型纳米制造方法，无需复杂的光刻即可为光学超材料创建大面积纳米结构。将超材料结构单片集成到光电探测器阵列集成电路 (IC) 基板上，无需光学透镜即可检测超材料增强荧光（目标 2）。定制 CMOS 光电探测器阵列 IC 还提供所有传感器的片上信号处理和数字化功能，同时提供简单的数字读出功能。多路复用传感器将通过集成传感器基板上的探针阵列的可寻址功能化来实现。使用共面晶圆级成型技术对传感器 IC 进行微流体传输封装，将为 POC 测试提供灵敏的小型化荧光检测平台（目标 3）。拟议的工作将阐明纳米尺度上光与物质相互作用的基本原理，创建新的生物传感技术，并为光学纳米结构、微流体和 CMOS IC 的集成设计指南，以实现广泛的未来应用。该奖项反映了 NSF 的法定使命，并具有通过使用基金会的智力优点和更广泛的影响审查标准进行评估，被认为值得支持。