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换，不仅在社会层面，而且在细胞层面都发挥着重要作用，促进了复杂性和智能的发展。随着生理功能和机制的日益复杂，科学家们在全面研究和理解它们方面面临着更大的挑战。体外模型提供了一种方法，通过忠实地复制相关的体内特征，同时在简单性和准确性之间取得平衡，从而提高实验结果的生物学相关性和统计稳健性，从而减轻这种复杂性。然而，这些模型的效用受到与这些模型通信的可用工具的限制，即调查和交互技术。鉴于人类和细胞使用的语言不同，一个类似于语言翻译器的双向界面对于实现细胞和人类之间的信息交换至关重要。生物电子学已经成为构建这种双向界面的一个有前途的途径，可以实现连续的、无标签的监测和精确的生物活动控制。生物电子学通过翻译细胞通信中的化学和电子信号，促进了对细胞过程的更深入的理解和更好的控制。与通常通过不频繁的测量和人工干预来评估的传统体外系统不同，双向界面的系统集成为开发复杂的工具开辟了新的途径，这些工具可以更深入地了解生物系统。此外，将生物电子学与仿生方法相结合利用了自然的解决方案，例如用于生物电子传感的信号转导膜受体与生物膜或电细胞刺激，从而弥合了生物学和电子学的强大能力。该项目的主要目标是在调节通路模型中双向仿生界面的系统集成，以探索体外人体生理学。虽然通过利用仿生生物电子学方法与生物结构接口的优势开发一个可以定制各种生理途径的平台是最终目标，但其能力的演示将通过最初专注于人类生理的一个特定系统途径来实现。肠脑轴是这样一个系统的一个有趣的候选者，考虑到它在全身的广泛连接和对信息处理的影响迹象，最近受到了大量关注。随着电子和化学信号在身体距离上的交换，这个系统提供了一个合适的复杂模型。具体来说，血清素通路以其深刻的全身作用为特征，对动物模型的孤立研究提出了挑战。开发一个模拟这一途径相关特征的平台将为肠道和大脑之间复杂的相互作用提供有价值的见解。因此，参与血清素通路的相关细胞系应该在微生理系统中共同培养，以体外模拟肠-脑轴的一个方面。同时，一个双向仿生界面，结合生物电子元件，如生物膜传感器和电细胞刺激，应该无缝集成，以实现连续监测和系统行为的精确调节。这里提出的平台有望促进我们对生命系统的理解和沟通能力，从而促进后续干预，并利用技术来增强知识和人类福祉。

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.