Electrochemical sensing in complex matrices

直接在复杂的基质中实现对分子库的具体测量，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，最终导致需要数小时/数天才能返回单一答案的繁琐和受实验室限制的方法。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，从而产生强烈的生化反应，尽管它所在的基质具有复杂的性质。她做到这一点在一定程度上要归功于构象选择，这是一种围绕识别目标分子后生物分子受体形状变化的检测方案。在这种前所未有的能力的启发下，凭借在分析电化学方面的独特专业知识，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机制。具体地说，我们感兴趣的是了解电极连接的生物分子受体的控制物理化学性质，这些性质影响它们识别分子和在这些基质中经历结合诱导的构象变化的能力。我们计划通过开发独创的电化学生物物理方法来研究这些系统，以帮助我们指导能够连续监测分子的创新的可推广、单步和无试剂的电分析传感平台的设计。我们特别感兴趣的是为那些由于其快速新陈代谢(即神经递质)而仍然难以以足够的时间分辨率进行测量的分子开发传感方法。作为回应，为了实现此类分子的高时间分辨率测量，我们计划开发电化学询问策略，以提供高时间分辨率测量，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率测量的技术。在复杂的基质中以足够的特异性测量神经递质也是一项挑战，我们计划通过开发依赖于引入非核酸大分子受体的新型电化学触发开关传感器来解决这一问题。我们认为，达到这些里程碑对于提高我们可以直接在未稀释的复杂矩阵中进行分子测量的特异度和灵敏度至关重要。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，用于前所未有的分子实时检测，而不是系统地求助于由训练有素的人员运行的繁琐、缓慢的实验室过程。

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