Electrochemical sensing in complex matrices

复杂基质中的电化学传感

• 批准号: RGPIN-2021-03974
• 负责人: DauphinDucharme, Philippe
• 金额: $ 1.75万
• 依托单位: Université de Sherbrooke
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=742799
• 关键词: Electrochemical; sensing; complex; matrices

Achieving specific measurements of libraries of molecules directly in complex matrices, like undiluted whole blood, remains an important socioeconomical challenge. This is because common detection strategies rely on multi-step and complex processes that ultimately lead to cumbersome and laboratory-bound approaches that require hours/days to return a single answer. Mother nature, in contrast, is able to efficiently detect molecules with exquisite specificities to produce strong biochemical responses in spite of the complex nature of the matrix in which it operates. She does so in part thanks to conformational selection, a detection scheme that revolves around the change in shape of a biomolecular receptor upon recognition of a target molecule. Inspired by this unprecedented capability and with a unique expertise in analytical electrochemistry, my research program aims to understand the mechanisms that limits our ability to artificially detect molecules directly in undiluted complex matrices. Specifically, we are interested in understanding the governing physicochemical properties of electrode-attached biomolecular receptors that influence their ability to recognize molecules and undergo binding-induced conformational change in these matrices. We plan to study these systems by developing original electrochemical biophysical approaches to help us guide the design of innovative generalizable, single-step and reagentless electroanalytical sensing platforms able to continuously monitor molecules. We are notably interested in developing sensing approaches for molecules that remain challenging to measure with sufficient temporal resolution due to their fast metabolism (i.e., neurotransmitters). In response, to achieve highly-time resolved measurements of such class of molecules, we plan to develop electrochemical interrogation strategies to afford highly-time resolved measurements, notably through the inception of electrochemical phase interrogation, a technique that achieves millisecond-resolved measurements. Neurotransmitters are also challenging to measure with sufficient specificity in complex matrices which we plan to address by developing new classes of electrochemically-triggered switch-based sensors that rely on the introduction of non-nucleic acid macromolecular receptors. We consider that reaching these milestones is essential to increase the specificity and sensitivity with which we can perform molecular measurements directly in undiluted complex matrices. We envision that these new classes of sensors will likely have an impact to address the socioeconomical need in developing unique, convenient and rapid personalized medicine approaches for unprecedented real-time detection of molecules as opposed to systematically resorting to cumbersome, slow laboratory-bound processes ran by trained personnel

直接在复杂基质中实现分子库的特定测量，如未稀释的全血，仍然是一个重要的社会经济挑战。这是因为常见的检测策略依赖于多步骤和复杂的过程，最终导致繁琐和实验室限制的方法，需要数小时/数天才能返回单个答案。相比之下，大自然母亲能够有效地检测具有精致特异性的分子，以产生强烈的生化反应，尽管它在其中运作的基质具有复杂的性质。她这样做部分归功于构象选择，这是一种围绕识别目标分子时生物分子受体形状变化的检测方案。受到这种前所未有的能力的启发，并在分析电化学方面拥有独特的专业知识，我的研究计划旨在了解限制我们直接在未稀释的复杂基质中人工检测分子的能力的机制。具体而言，我们有兴趣了解电极连接的生物分子受体，影响其识别分子的能力，并在这些矩阵中进行绑定诱导的构象变化的管理物理化学性质。我们计划通过开发原始的电化学生物物理方法来研究这些系统，以帮助我们指导创新的可推广的，单步和无试剂的电分析传感平台的设计，从而能够连续监测分子。我们特别感兴趣的是开发用于分子的传感方法，这些分子由于其快速代谢（即，神经递质）。作为响应，为了实现此类分子的高时间分辨测量，我们计划开发电化学询问策略以提供高时间分辨测量，特别是通过电化学相位询问的开始，这是一种实现毫秒分辨测量的技术。神经递质也具有挑战性，以足够的特异性在复杂的矩阵，我们计划通过开发新的类的电化学触发的开关为基础的传感器，依赖于非核酸大分子受体的引入来解决测量。我们认为，达到这些里程碑是必不可少的，以提高特异性和灵敏度，我们可以直接在未稀释的复杂基质中进行分子测量。我们设想，这些新型传感器可能会产生影响，以满足社会经济需求，开发独特，方便和快速的个性化医学方法，以实现前所未有的实时分子检测，而不是系统地诉诸于由训练有素的人员运行的繁琐，缓慢的实验室过程