Spatiotemporal control of concentration gradients with electrochemistry in extracelluar space

细胞外空间电化学浓度梯度的时空控制

• 批准号: 10664955
• 负责人: Chong Liu
• 金额: $ 37.11万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10664955
• 关键词: Affect; Algorithms; Chemicals; Chemistry; Devices; Dioxygen; Disease; Electrochemistry; Electrodes; Ensure; Environment; Heterogeneity; In Vitro; Individual; Inorganic Chemistry; Length; Machine Learning; Methods; Microbial Biofilms; Microelectrodes; Microscopic; Mission; Nature; Oxidation-Reduction; Property; Public Health; Reaction; Reactive Oxygen Species; Research; Shapes; Social Behavior; Spatial Distribution; Specificity; Surface; System; Transition Elements; United States National Institutes of Health; Work; biomaterial compatibility; combat; extracellular; gut microbiota; microbial; microbiota; microorganism; microorganism culture; nano; nanomaterials; programs; response; simulation; spatiotemporal; spectroscopic imaging; technology development; tool

Project Summary The natural environment is intrinsically spatiotemporally heterogenous at both macroscopic and microscopic levels. What shapes such a heterogeneity includes the concentration gradients of biologically relevant chemical species in the extracellular medium including dioxygen (O2), reactive oxygen species (ROS), as well as essential redox-active transition metals. While a significant amount of effort has been devoted to spectroscopically image these chemical moieties, our capability to spatiotemporally control their concentration distributions in the extracellular medium remains limited. This is especially the case for biofilms and microbiota, in which the microorganisms’ small length scales pose significant challenges for concentration modulation. The inadequate control of concentration heterogeneity limits our capability of mimicking the natural environments in vitro and investigating how local concentration gradients affect microbial functionality. Therefore, there is a need for an advanced method of controlling chemical concentrations at microscopic level. Our proposed research aims to use electrochemical nano-/micro-electrodes to spatiotemporally control the concentration gradients in the extracellular medium. When an electrochemical reaction occurs on an electrode’s surface, a concentration gradient is established near the electrode. Taking advantages of this phenomena with the assistance of numerical simulation, we will employ an array of nano-/micro-electrodes with individually addressable electrochemical potentials to program any arbitrary spatiotemporal concentration profiles. We will fine-tune the surface chemistry and the electrochemical properties of these electrodes to ensure biocompatibility and reaction specificity. The developed system will be applied to biofilms and we aim to investigate how the microbial social behavior will be affected by a perturbation of local O2 concentration. Moreover, we will use this device to mimic the heterogenous environment in the gut and culture gut microbiota in vitro. An algorithm based on machine learning will be employed to actively adjust electrode potentials, maintaining a stable concentration profile despite the accumulation of gut microorganisms. Ultimately, our work will expand our capability of controlling the concentration heterogeneity in nature. The developed electrochemical system will serve an in vitro platform to culture microorganisms in their native environment, or as a tool to perturb the concentration profiles. Combining electrochemistry, inorganic chemistry, and nanomaterials the research will enable a deeper understanding of the spatial distribution and temporal response of microbial systems.

项目摘要 自然环境在宏观和 微观水平。这种异质性的形状包括生物学上的浓度梯度 细胞外培养基中的相关化学物种，包括二氧化物（O2），活性氧（ROS）， 以及必需的氧化还原活性过渡金属。虽然大量的努力已致力于 光谱镜图像这些化学部分，我们的空间临时控制其浓度的能力 细胞外培养基中的分布仍然有限。生物膜和微生物群尤其是这种情况， 其中微生物的小长度对浓度调节构成了重大挑战。 对浓度异质性的控制不足，我们模仿自然的能力 体外环境并研究局部浓度梯度如何影响微生物功能。 因此，需要采用先进的方法来控制微观水平的化学浓度。 我们提出的研究旨在使用电化学纳米/微电极进行时空 控制细胞外培养基中的浓度梯度。当电化学反应发生在 电极表面，浓度梯度在电极附近建立。利用这一点 在数值模拟的帮助下，我们将采用一系列纳米/微电极 具有单独寻址的电化学潜力来编程任何任意时空 浓度曲线。我们将微调这些化学和这些的电化学特性 电极以确保生物相容性和反应特异性。开发的系统将应用于生物膜 我们旨在调查微生物社会行为将如何受到本地O2的扰动的影响 专注。此外，我们将使用此设备模仿肠道和培养的异质环境 体外肠道菌群。将聘请基于机器学习的算法以主动调整电气 电势，保持稳定的浓度曲线DOS肠道微生物的积累。 最终，我们的工作将扩大我们控制自然界浓度异质性的能力。 开发的电化学系统将在其本地培养微生物的体外平台 环境，或作为扰动浓度轮廓的工具。结合电化学，无机 化学和纳米材料这项研究将使对空间分布和 微生物系统的临时响应。