Innovating Bioanalytical Technologies using Bioinspired Nanomaterials

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Innovating Bioanalytical Technologies using Bioinspired Nanomaterials Proteins are central to many important biological processes such as regulating cellular pathways, catalyzing metabolic reactions, and tumorigenesis. Quantifying protein levels in cells and biofluids is critical to characterizing protein function and regulation of biological processes. The proposed research program will innovate protein-assay technologies using bioinspired nanomaterials to pursue our vision of solving fundamental and applied challenges in bioanalytical chemistry. This research program is inherently interdisciplinary and will support a diverse team of analytical chemists, material chemists, clinical chemists, engineers, biologist, and medical scientists. This NSERC Discovery Grant proposal will support seven graduate students and we will achieve our program goals through three objectives: Objective 1: Identify fundamental principles of biological and bioinspired material formation pathways. We aim to strategically design bioinspired nanomaterials for protein assays using material formation-structure-function principles. We hypothesize that nanoscale interactions and phases dictate formation pathways and direct the nanomaterial structure and function. We propose to study the formation and function of biomineral and bioinspired nanomaterials using a new complementary approach that integrates single-molecule fluorescence and cryotransmission electron microscopy. In the short term, we will investigate the formation mechanisms of enzyme-based calcium phosphate and of catalytically-active metal-organic frameworks (MOFs). Objective 2: Demonstrate proof-of-concept complementary, single-molecule assays for protein analyses. Many proteins that are involved in important biological processes exist at very low concentrations and require methodologies sensitive enough to detect a low number of molecules. My lab will develop new single-molecule technologies that can achieve ultrasensitive quantification of more than one protein property. In the short term, we will develop two proof-of-concept assays for the complementary analysis of enzyme concentration and activity based on (1) metal nanoparticles and (2) MOF nanozymes. Objective 3: Develop electrochemical biosensors based on bioinspired nanomaterials for multiplexed protein detection. Real-time protein measurements can provide dynamic information on the physiological state of a biological system and can be obtained via quantitative biosensors with rapid response times. In the short term, my lab will develop electrochemical biosensors based on MOF-antibody composites for rapid detection of highly-abundant proteins in biofluids. We aim to achieve simple workflows, high sensitivity, rapid response times, and multiplexed protein measurements.