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 自然环境在宏观和宏观上都具有内在的时空异质性。 微观层面。形成这种异质性的因素包括生物上的浓度梯度 胞外介质中的相关化学物种包括氧气(O2)、活性氧(ROS)、 以及必需的氧化还原活性过渡金属。虽然已经投入了大量的努力来 通过光谱成像这些化学成分，我们在时空上控制它们浓度的能力 在细胞外培养液中的分布仍然有限。对于生物膜和微生物区系来说尤其如此， 其中微生物的小长度尺度对浓度调节构成了巨大的挑战。 对浓度异质性的不充分控制限制了我们模仿自然的能力 并研究局部浓度梯度如何影响微生物功能。 因此，需要一种先进的方法在微观水平上控制化学浓度。 我们提出的研究旨在利用电化学纳米/微电极在时空上 控制细胞外培养上清液的浓度梯度。当电化学反应发生在 在电极表面，在电极附近建立了浓度梯度。利用这一点 现象在数值模拟的辅助下，我们将使用纳米/微电极阵列 具有可单独寻址的电化学势以编程任意时空 浓度分布。我们将微调这些材料的表面化学和电化学性质 电极，以确保生物兼容性和反应专一性。所开发的系统将应用于生物膜 我们的目标是调查微生物的社会行为将如何受到局部O2扰动的影响 集中精神。此外，我们将使用这个设备来模拟肠道和培养中的异质环境 肠道微生物区系的体外研究。采用基于机器学习的算法对电极进行主动调整 潜力，尽管肠道微生物积累，但仍保持稳定的浓度分布。 最终，我们的工作将扩大我们控制自然界中浓度异质性的能力。 开发的电化学系统将为在其本土培养微生物提供一个体外平台 环境，或作为扰乱浓度分布的工具。结合电化学，无机化学 化学和纳米材料的研究将使我们能够更深入地了解空间分布和 微生物系统的时间响应。