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.
