Mobile phone imaging of fluorescence assays in scattering media

Abstract

Recent efforts to translate diagnostic tests from laboratories to the point of care have yielded countless assays used in clinics and even the home. Point-of-care tests enable earlier diagnosis, potentially improving patient outcomes, reducing superfluous medical procedures, and lowering healthcare costs. Home assays such as lateral flow tests for pregnancy or HIV prioritize low cost and ease of use, typically by labeling antibodies with chromophores in a highly scattering porous substrate. These home assays suffer from poor sensitivities, in part due to the low contrast optics underlying the assay. In contrast, extant laboratory tests are highly sensitive molecular assays that detect fluorescence-labeled biomarkers with costly onboard electronics. The recent proliferation of low-cost consumer electronics suggests a path toward translating the benefits of laboratory assays to the home, especially by leveraging the advanced camera hardware in modern smartphones to image fluorescence-labeled assays. However, several factors impede the naïve implementation of fluorescence assays in the porous media in which home assays are performed, particularly light scattering and autofluorescence in porous media and the need for costly optical filters. This dissertation overcomes these challenges with multiple algorithmic, electronic, engineering, and chemistry innovations that together enable mobile phone fluorescence imaging in porous media. This work focuses particularly on sample-agnostic fluorescence imaging of both protein and nucleic acid biomarkers and is a step toward translating fluorescence assays to the home.