Cellular level cryo-neuromodulation using rapid and localized cooling device combined with microelectrode array

Abstract

Cryotherapy, a rapid and effective medical treatment utilizing low temperatures, has not been widely adopted in clinical practice due to a limited understanding of its mechanisms and efficacy. This challenge stems from the absence of methods for fast, precise, and localized spatiotemporal temperature control, as well as the lack of reliable real-time quantitative techniques for measuring and analyzing the effects of cooling. To address these limitations, this study introduces a cryo-neuromodulation platform that integrates a high-speed precision cooling device with a microelectrode array (MEA) system. This platform enables the investigation of cellular-level cryo-modulation of neuronal activity and its effects on surrounding cells, providing a novel framework for advancing research in cryotherapy and neuromodulation. Experiments show that neurons recovered fully within 1 min of cooling with a fast-cooling rate (−20 °C/s at cooling) and that silenced neurons can influence distant cells via a well-organized network. Extended cooling durations (e.g., 10 min) resulted in altered neuronal dynamics, including delayed recovery and reduced burst activity, highlighting the importance of precise control over cooling parameters. This device offers reversible neural control, with potential applications in both research and clinical settings, such as anesthesia, pain management and treatment of neurological disorders like neocortical seizures.