Spatiotemporal control of concentration gradients with electrochemistry in extracelluar space

采购微流控装置用落射荧光显微镜的行政补充 项目摘要 已获拨款的项目简介（R35 GM 138241项目摘要） 自然环境在宏观和微观两个方面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学上的浓度梯度， 细胞外介质中的相关化学物质，包括分子氧（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， 对这些化学成分进行光谱成像，我们时空控制其浓度能力 在细胞外介质中的分布仍然有限。对于生物膜和微生物群尤其如此， 其中微生物的小长度尺度对浓度调节提出了重大挑战。 浓度不均匀性的控制不足限制了我们模仿自然环境的能力。 在体外环境和调查如何局部浓度梯度影响微生物的功能。 因此，需要一种在微观水平上控制化学品浓度的先进方法。 我们提出的研究旨在使用电化学纳米/微电极时空 控制细胞外介质中的浓度梯度。当发生电化学反应时， 在电极的表面上，在电极附近建立浓度梯度。利用这一点 在数值模拟的帮助下，我们将采用纳米/微米电极阵列 利用可单独寻址的电化学电势， 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，以确保生物相容性和反应特异性。所开发的系统将应用于生物膜 我们的目标是研究微生物的社会行为将如何受到当地O2扰动的影响 浓度.此外，我们将使用该装置模拟肠道和培养物中的异质环境， 体外肠道菌群。将采用基于机器学习的算法来主动调整电极 潜在的，保持稳定的浓度曲线，尽管肠道微生物的积累。 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。 所开发的电化学系统将作为体外平台在其天然环境中培养微生物。 环境中，或作为一种工具，扰乱浓度分布。结合电化学、无机 化学和纳米材料的研究将使人们能够更深入地了解空间分布， 微生物系统的时间响应。

Administrative supplement to purchase an epifluorescence microscope for microfluidic devices Project Summary Description of Funded Grant (Project Summary for R35 GM138241) 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.