Rotation 1: Microelectrode arrays for astrocyte electrophysiology

BBSRC战略主题：变革性技术通信被定义为实体之间的信息交流，不仅在社会层面而且在细胞层面上发挥着重要作用，促进了复杂性和智能性的发展。随着生理功能和机制的日益复杂，科学家在全面研究和了解它们方面遇到了更大的挑战。体外模型提供了一种缓解这种复杂性的方法，它忠实地复制了体内的相关特征，同时在简单性和准确性之间取得了平衡，从而提高了实验结果的生物学相关性和统计稳健性。然而，这些模型的实用性受到可用于与这些模型交流的工具的限制，即调查和互动技术。鉴于人类和细胞使用不同的语言，一个类似于语言翻译器的双向接口对于实现细胞和人类之间的信息交换是必不可少的。生物电子学已经成为构建这种双向接口的一种有前途的途径，使连续的、无标记的监测和对生物活性的精确控制成为可能。通过翻译化学和电信号，这两个在细胞通讯中的关键角色，生物电子学促进了对细胞过程的更深入的理解和更好的控制。与传统的体外系统不同，传统的体外系统通常通过不频繁的测量和人工干预进行评估，双向接口的系统集成为开发复杂的工具开辟了新的途径，这些工具可提供对生物系统的更深入了解。此外，将生物电子学与仿生方法相结合，利用自然界的解决方案，如用于生物电子传感的膜受体，与生物膜或电细胞刺激相结合，从而将生物和电子的强大能力联系起来。该项目的主要目标是在调节通路模型中系统集成双向仿生界面，以探索体外人类生理学。虽然开发一个可以利用仿生生物电子方法的优势与生物结构对接的平台是最终目标，但其能力的展示将通过最初专注于人类生理的一种特定系统途径来实现。肠道-脑轴是这种系统的一个有趣的候选者，因为它在全身广泛连接，并显示出对信息处理的影响，这最近受到了极大的关注。通过跨越身体距离交换电子和化学信号，该系统提供了一个恰如其分的复杂模型。具体地说，以其深刻的全身作用为特征的5-羟色胺途径，对动物模型的单独研究提出了挑战。开发一个模拟这一途径的相关特征的平台将为深入了解肠道和大脑之间的复杂相互作用提供有价值的见解。因此，参与5-羟色胺途径的相关细胞系应该在微生理系统中进行共培养，以在体外模拟肠道-脑轴的一个方面。同时，一个包含生物电子元件(如生物膜传感器和电细胞刺激)的双向仿生界面应无缝集成，以实现对全身行为的持续监测和精确调节。这里提出的一个平台有望增进我们对生命系统的理解和沟通能力，从而促进后续干预，并利用技术来增进知识和人类福祉。

BBSRC strategic theme: Transformative technologiesCommunication, defined as the exchange of information between entities, plays an essential role not only at the societal but also cellular level, facilitating the progression of complexity and intelligence. As physiological functions and mechanisms become increasingly sophisticated, scientists encounter greater challenges in comprehensively investigating and understanding them. In vitro models offer a means to alleviate this complexity by faithfully replicating relevant in vivo characteristics while striking a balance between simplicity and accuracy, thereby enhancing biological relevance and statistical robustness of experimental outcomes. However, the utility of these models is constrained by the tools available for communicating with these models, i.e. investigation and interaction techniques. Given the distinct languages spoken by humans and cells, a bidirectional interface, akin to a language translator, is essential to enable the exchange of information between cells and humans. Bioelectronics has emerged as a promising avenue for constructing such bidirectional interfaces, enabling continuous, label-free monitoring and precise control of biological activity. By translating chemical and electrical signals, both pivotal players in cellular communication, bioelectronics facilitates a deeper understanding of and better control over cellular processes. Unlike conventional in vitro systems, which are often assessed through infrequent measurements and manual interventions, system integration of bidirectional interfaces opens new avenues for developing sophisticated tools that provide deeper insights into biological systems. Moreover, combining bioelectronics with biomimetic approaches leverages nature's solutions such as membrane receptors for signal transduction utilised in bioelectronic sensing with biomembranes or electrical cell stimulation, thereby bridging the formidable capabilities of biology and electronics. The primary objective of this project is the system integration of bidirectional biomimetic interfaces in regulatory pathway models to explore human physiology in vitro. While developing a platform that can be tailored to various physiological pathways by leveraging the advantages of biomimetic bioelectronic approaches for interfacing with biological structures presents the ultimate goal, demonstration of its capabilities will be achieved by initially focusing on one specific systemic pathway of human physiology. The gut-brain axis presents an intriguing candidate for such a system, given its widespread connections throughout the body and indications of influence on information processing, which recently received a great deal of attention. With electrical and chemical signals exchanged across bodily distances, this system offers a fittingly complex model. Specifically, the serotonin pathway, characterised by its profound systemic effects, poses challenges for isolated investigation in animal models. Developing a platform that mimics relevant features of this pathway would provide valuable insights in the complex interplay between gut and brain.Thus, relevant cell lines involved in the serotonin pathway should be co-cultured within a microphysiological system to model a facet of the gut-brain axis in vitro. Concurrently, a bidirectional biomimetic interface, incorporating bioelectronic elements such as biomembrane sensors and electrical cell stimulation, should be seamlessly integrated to enable continuous monitoring and precise modulation of systemic behaviour. A platform as the one proposed here holds promise for advancing our understanding of and communication capabilities with living systems, which facilitates subsequent interventions and leverages technology to enhance knowledge and human well-being.