Division Session “Soft-nanotechnology for brain science and biological systems” was organized at JVSS 2023 by the Division of Soft-Nanotechnology at the Japan Society of Vacuum and Surface Science. The current Special Issue gathers review articles authored by the five invited speakers of the Session.

The rapid advancement of software-based deep learning has led to a surge in AI applications, yet hardware limitations in silicon CMOS technology hinder performance. Consequently, interest is growing in hardware technologies and new materials for artificial neural networks (ANNs) and neuromorphic systems. Exploiting nanomaterials nonlinearity caused by spontaneous physical phenomena holds promise of reducing power consumption in AI hardware. Reservoir computing devices, derived from recurrent neural networks, play a crucial role, with material reservoir devices showcasing “material intelligence.” Tailored nanomaterials for reservoir devices hold potential for revolutionizing AI, especially in robotics. As research progresses, focusing on device functionalization and applications, recent findings underline the significance of integrating nanomaterials into AI hardware for enhanced computational capabilities and energy efficiency.

In recent years, many researchers have proposed biohybrid systems that integrate biological materials, especially cells or cultured tissues formed by in vitro cell culture, and microdevices to utilize the functions of cultured cellular tissues in an engineering way. In this paper, we focus on microphysiological systems composed of microfluidic channels or microdevices and cells or cultured tissues and introduce the functional characteristics of these microphysiological systems. In the microphysiological system, we can adjust cell culture conditions under mechanical stress control and bring out the dynamic performance of the cultured tissue. The systems can be applied not only to drug development to replace laboratory animals, but also to the development of advanced robots with cellular functions. Therefore, we believe that the biohybrid systems are a promising technology to apply cells and cultured tissues in various fields.

The selection of experimental specimens is critical for elucidating brain function. Specimens used in brain research range from in vivo (individual level) to in vitro (culture level). Recently, in vivo research has been particularly popular, considered an ideal experimental system for observing brain functions in real time and elucidating physiological functions without harming individuals. However, in vivo specimens, which form complex neural circuits, also have drawbacks, including 1) difficulty in data analysis and interpretation of phenomena ; 2) limitations in experimental manipulation and control of neural circuits ; 3) the number of cases cannot be easily obtained due to the required skill in conducting experiments ; and 4) animal welfare issues. On the other hand, an in vitro model introduced in this issue offers the advantage of artificially simplifying the model, enabling a more precise and accurate analysis of brain functions in vitro. This paper presents an autapse culture preparation using single neurons.

Human pluripotent stem cells, including embryonic stem cells and induced pluripotent stem cells, are emerging as new scientific fields for understanding the pathology of human diseases, regenerative medicine, and drug discovery. In recent years, advanced technologies for cell culture and neuronal differentiation of human cells have provided stable and reproducible methods, contributing to the development of new cross-disciplinary scientific trends alongside various research technologies. Here, we introduce our recent research on brain region-specific neuronal differentiation and brain organoid induction from human pluripotent stem cells, as well as their application for disease modeling and regenerative medicine. Furthermore, we discuss the future direction and application of human pluripotent stem cell technology in advancing scientific discovery.

Three-dimensional (3D) cultured cells, such as spheroids and organoids, have been recognized as highly relevant in vitro tissue models. In addition, recent advances in microfabrication techniques have facilitated the development of microphysiological systems (MPS), in which cells are cultured in a microfluidic device that mimics the physiological environment and promotes the development of tissue-like structures. To make effective use of these in vitro models, techniques are needed that can assess the activities of the cells. Electrochemical sensors are promising due to their ease of miniaturization, label-free and real-time measurement of cell-derived molecules. Here we review the electrochemical assessment of 3D cultured cells using different types of electrochemical devices such as probe electrodes, electrode arrays, and electrochemical imaging methods. In addition, recent advances in the integration of electrochemical sensors into MPS are presented. Finally, the challenges and prospects for advancements in 3D culture systems integrated with electrochemical devices are discussed.