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

Princeton University, Princeton NJ

Investigators

Abstract

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.