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Computational Sensing in Biophotonics and Diagnostics

Abstract

Over the past decades the dramatic increase in computational resources coupled with the advent of machine learning and artificial intelligence has profoundly impacted sensor technology. Together, these trends present a new opportunity for data-driven computational sensor design, where acquisition hardware is fundamentally changed to “lock-in” to the optimal sensing data with respect to a user defined cost function. This dissertation addresses this emerging opportunity, referred to herein as computational sensing, with a focus on applications in biophotonics and diagnostics where there is currently high-demand for cost-effective and

compact sensing systems for democratizing global health. Therefore, several examples of computational sensing systems will be presented, all of which leverage machine learning and data-driven design principles to enable low-cost, compact, and sparse implementations well-suited for the point-of-care among other settings.

Firstly, I will discuss a multiplexed paper-based vertical flow assay and reader for biomarker quantification at the point-of-care. I will show how deep learning and statistical analysis of the multiplexed sensor response can be leveraged to improve accuracy, dynamic range, and limit-of-detection, greatly enhancing the sensing capabilities beyond that of the traditionally employed lateral flow assay. Additionally, I will demonstrate feature selection techniques which can serve as a toolbox for iterative assay development, sensor design, and cost-performance optimization. Two applications in point-of-care diagnostics will be presented with this platform, one being a clinical study for early-stage Lyme Disease diagnoses, and the other, a clinical study for cardio-vascular risk assessment by the high-sensitivity C-Reactive Protein test. Secondly, Localized plasmon resonance (LSPR) sensors and their corresponding readers will be discussed as computational sensing systems for label-free biomolecular sensing. Through machine learning of spectral characteristics, I will present how the corresponding LSPR sensor reader can be jointly designed with the LSPR sensor to optimize read-out accuracy while minimizing cost by computationally selecting from cost effective illumination optics. Lastly, a fundamentally different hardware design for spectroscopy, enabled by deep learning, will be demonstrated and discussed for application-specific performance advantages in terms of acquisition rate, form factor, and cost.

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