EAGER: 3D Electroluminescent Living Cellular Devices (ELICD) for Multicellular Systems Biology Research

[1638753] koomson在适合多细胞系统生物学研究的脑功能基本原理和临床研究之间存在着很大的差距，因为无论是单细胞还是整个器官/生物体为基础的仪器都不能提供生物学和临床相关性的数据。目前的研究方法要么集中在分子上，要么集中在整个器官的功能上，而现有的方法要么是非自然的，比如基因修饰，要么缺乏深度，无法理解大脑是一个由数百万种不同类型的细胞组成的系统。这个探索性项目的目标是设计、开发和实施一种新型的“活细胞装置”，将3D大脑皮层细胞培养物整合在丝绸支架中，与纳米级光学和电子装置相结合，以报告长时间内细胞的实时电活动数据。这项计划中的研究是第一次将生物金属电致发光作为生物研究的工具，并监测/调节脑细胞系统的电活动。该仪器的设计利用了丝素等坚固的双光子材料的独特光学和物理特性，在实现3D光学元件和制造用于皮质组装集成的多孔组织支架方面显示出巨大的前景。这种新设备将在各种科学和工程领域产生更广泛的影响，包括疾病途径、药物开发和基于正确理解生物过程和干预因素的生物工程。光电技术在生物医学，尤其是成像和诊断领域有着广泛的应用。基础科学知识与临床知识的结合对于推动转化研究领域向有针对性的发现、诊断和治疗方向发展是必要的。基础和临床研究实验室之间的主要差距是适合多细胞系统生物学研究的技术，因为无论是单细胞还是整个器官/生物体的设备都不能同时提供多细胞系统动力学和生物过程的临床相关信息。因此，首先有必要开发集成的生物设备，提供生物学和临床相关的数据。该项目的目标是设计、开发和实现一种新型光电器件，将生物相关的3D大脑皮层细胞培养物与纳米级电致发光锆电子技术相结合，以报告长时间内细胞的实时电活动数据。该项目是第一个使用生物金属电致发光作为生物研究的工具，并监测/调节脑细胞系统的电活动。这项研究将有助于神经技术作为基础研究和临床研究之间的桥梁，将生物学、医学、工程学和材料科学的工具和原理结合起来。开发的“活细胞装置”将是第一个自我报告的、无创的、生物/临床相关的、毫米大小的生物电子系统，用于体外和体外的基础脑研究。锆的电致发光特性将被研究和表征，随后确定器件内电和光组件之间相互作用的范围。研究将集中于检测细胞静息膜电位（几种生物过程的内在调节剂）动态产生的细胞外电场的变化，范围从远距离低量级到毫秒级变化。该领域目前使用的方法侧重于光转换为电信号，而拟议的研究将通过将电信号转换为光而以非侵入性的方式改变传统。所提出的仪器设计利用了丝素等强大双光子材料独特的光学和物理特性，在实现3D光学元件和制造用于皮质组装集成的多孔组织支架方面显示出巨大的前景。这种新型光电器件将在各种科学和工程领域产生重大而广泛的影响，从药物开发到基于对生物过程和干预因素的正确理解的生物工程。这项研究将展示一种独特的神经工程设计，它将允许以一种成本和时间有效的方式研究大脑功能，同时与使用实验室动物或没有生物成分的工具相比，保持高度的生物学相关性。

1638753 - KoomsonThere exists a wide gap between basic principles of brain function and clinical research suitable for multicellular systems biology research because neither the single cell- nor the whole organ/organism-based instruments can provide data on both biological and clinical correlation. Current research methodologies focus either on molecular or on the whole organ function, and existing methods are either unnatural, such as genetic modifications, or lack the depth to understand the brain as a system made of many million cells of different types. The objective of this exploratory project is to design, develop and implement a new class of "living cellular devices", combining 3D cerebral cortical cell cultures integrated in silk scaffolds with nanoscale optical and electronic devices to report data on real-time electrical activity of cells over long periods of time. The planned research is the first to use biometal-electroluminescence as a tool in biological research and to monitor/modulate electric activity of brain cellular systems. The instrument design exploits the unique optical and physical properties of robust biphotonic materials such as silk fibroin, which has shown great promise in realizing 3D optical elements, and fabrication of porous tissue scaffolds for cortical assembly integration. The new device will have significant broader impacts in various science and engineering areas, ranging from disease pathways, drug development and bioengineering based on correct understanding the biological processes and the intervening factors. Optoelectronic technologies are often applied in biomedicine, especially in imaging and diagnostics. The combination of basic scientific knowledge with clinical knowledge is necessary to advance the field of translational research towards well-targeted discoveries, diagnostics and treatments. The main gap between the basic and clinical research laboratories are the technologies suitable for multicellular systems biology research because neither the single cell- nor the whole organ/organism-based devices can inform on both multicellular systems dynamics and clinical correlates of the biological process. Thus it is first necessary to develop integrated biological devices providing data with both biological and clinical correlation. The objective of this project is to design, develop and implement a new class of optoelectronic devices, combining biologically-relevant 3D cerebral cortical cell cultures homed in silk scaffolds with nanoscale, electroluminescent Zirconium electronics to report data on real-time electrical activity of the cells over long periods of time. The project is the first to use biometal-electroluminescence as a tool in biological research and to monitor/modulate electric activity of brain cellular systems. The research will contribute to neural technologies as a bridge between basic- and clinical-research using a combination of tools and principles from biology, medicine, engineering and material science. The "living cellular devices" developed will be the first self-reporting, noninvasive, biologically/clinically relevant and millimeter-size bioelectronic systems to be used in fundamental brain research ex vivo and in vitro. Electroluminescence properties of Zirconium will be investigated and characterized, following with determining the range of interaction between the electric and the light components within the device. The studies will focus on detecting the changes in extracellular electric fields generated by the dynamics of cell resting membrane potential (an intrinsic regulator of several biological processes) ranging from long-range low magnitude to millisecond-speed changes. Current methodologies used in the area focus on conversion of the light into the electric signal while the proposed research will reverse the convention by converting the electric signal into light and this in a noninvasive manner. The proposed instrument design exploits the unique optical and physical properties of robust biphotonic materials such as silk fibroin, which has shown great promise in realizing 3D optical elements, and fabrication of porous tissue scaffolds for cortical assembly integration. The new optoelectronic device will have significant broader impacts in various science and engineering areas, ranging from drug development and bioengineering based on correct understanding of the biological processes and the intervening factors. The research will demonstrate a unique neuroengineering design that will allow studying brain functions in a cost- and time effective manner while keeping the high biological relevancy compared to the use of the laboratory animals or tools without biological components.