Innovating Bioanalytical Technologies using Bioinspired Nanomaterials

利用仿生纳米材料创新生物分析技术

• 批准号: RGPIN-2022-05239
• 负责人: Ogata, Alana
• 金额: $ 1.82万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=748359
• 关键词: Innovating; Bioanalytical; Technologies; using; Bioinspired

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.

蛋白质是许多重要生物过程的核心，如调节细胞通路、催化代谢反应和肿瘤发生。定量细胞和生物体液中的蛋白质水平对于表征蛋白质功能和生物过程的调节至关重要。拟议的研究计划将利用生物启发纳米材料创新蛋白质分析技术，以实现我们解决生物分析化学基础和应用挑战的愿景。这个研究项目本质上是跨学科的，将支持一个由分析化学家、材料化学家、临床化学家、工程师、生物学家和医学科学家组成的多元化团队。这项NSERC发现基金提案将支持7名研究生，我们将通过三个目标实现我们的项目目标：目标1：确定生物和生物启发材料形成途径的基本原则。我们的目标是利用材料形成-结构-功能原理战略性地设计生物启发纳米材料用于蛋白质分析。我们假设纳米尺度的相互作用和相决定了纳米材料的形成途径，并指导了纳米材料的结构和功能。我们建议使用一种新的互补方法，将单分子荧光和低温透射电子显微镜相结合，研究生物矿物和生物启发纳米材料的形成和功能。在短期内，我们将研究酶基磷酸钙和催化活性金属有机框架（MOFs）的形成机制。目的2：演示用于蛋白质分析的互补单分子分析的概念验证。许多参与重要生物过程的蛋白质存在于非常低的浓度，需要足够灵敏的方法来检测少量的分子。我的实验室将开发新的单分子技术，实现对多种蛋白质特性的超灵敏定量分析。在短期内，我们将基于(1)金属纳米颗粒和(2)MOF纳米酶开发两种概念验证分析方法，用于酶浓度和活性的互补分析。目的3：开发基于生物启发纳米材料的电化学生物传感器，用于多路蛋白检测。实时蛋白质测量可以提供生物系统生理状态的动态信息，并且可以通过具有快速响应时间的定量生物传感器获得。在短期内，我的实验室将开发基于mof抗体复合材料的电化学生物传感器，用于快速检测生物体液中丰富的蛋白质。我们的目标是实现简单的工作流程，高灵敏度，快速响应时间和多路蛋白质测量。