Grant: Discovery Grants Program - Individual

The detection and quantification of molecular markers of health, disease, and infection is essential for health care, personalized medicine, and public health. In practice, these measurements require specialized facilities with large and expensive equipment and specially trained personnel. This requirement creates substantial inequity in access and quality of health care, both between different countries and between different communities or social groups within a country. Advances in both policies and technologies are needed to address these problems. Molecular diagnostic technology that is easy to use, portable, and low cost (a.k.a. point-of-care diagnostics) will be essential for realizing quality health care as a globally accessible human right. Here, we propose new materials, methods, and devices for molecular diagnostics, alongside multidisciplinary training of three levels of HQP. This research will leverage our leadership in developing and implementing fluorescent nanoparticle (NP) materials to enable bioanalysis with smartphone-based devices. Our aims are to address unmet needs for point-of-care diagnostics, particularly with respect to key functional requirements: high sensitivity, multiplexing (i.e. parallel detection of multiple biomarkers), mix-and-measure capability (i.e. little or no user actions), quantitation without user calibration, sustainability, and optimized material properties. Some of the proposed research will leverage super-NP assemblies of quantum dots (super-QDs) that exhibit ultra-bright fluorescence, robust stability, and specific binding as immunoconjugates. We will develop mix-and-measure, calibration-free digital assays for protein biomarker and virus detection--without the compartmentalization, enzymatic amplification, or high-technology requirements of current methods. This assay and other assays will be ported from laboratory instruments to smartphone-based devices capable of total internal reflection fluorescence (TIRF), and benefit from new low-valent, clickable, and biofluid-compatible super-QDs. The methodology will also be extended to super-NP assemblies of other materials for enhancement of their special size-limited properties: magnetic NPs, silicon nanocrystals, and gold NPs. The new super-NPs will provide better sustainability and new opportunities and for fluorescence- and Raman-based bioanalyses. With the goal of reducing environmental impact, other research will design and optimize next-generation fluorescent NPs for future digital assays, smartphone-based diagnostics, and other applications in bioanalysis and imaging. These innovative materials will be derived from single dextran chains and aggregation-induced emission dyes, and from scaffolded J-aggregate nanoparticles with spectral properties tailored by energy transfer. Overall, the research explores new, impactful ideas for functional materials, assay methods, and devices with transformative potential for future molecular diagnostics.