Multimodal spatiotemporal drug assessment platform based on a microelectrode neural network chip in Alzheimer’s disease

Abstract

The pathogenesis of Alzheimer’s disease (AD) remains elusive. The development of new drugs is protracted, costly, and fraught with failure, largely due to the lack of convenient methods for dynamically studying the pathogenesis of AD and evaluating drug efficacy in vitro. There is a dearth of in vitro multi-site assay platforms capable of observing the therapeutic effects of AD drugs at the level of cellular and network. Consequently, an in vitro multimodal spatiotemporal drug assessment platform has been developed based on a neuronal network chip. It has a symmetric distribution of electrode points with two different sizes (10 μm and 30 μm), which are more suitable for the detection of neuronal connections. The multifaceted neurophysiological properties, including single neuron firing pattern, intercellular connection, transmission speed, and neural network communication, were detected in real time. The results demonstrated that the differences between experimental groups in electrophysiological properties, could significantly distinguish the effects of AD representative drug treatment after different levels of neurological injury. The administration of the drug at the initial stage of β-amyloid oligomers (AβOs) toxicity was found to effectively retard the deterioration of neurons and network (early stage: firing rate increased by 8 %; middle stage: cross-correlation coefficient decreased by 27 %; late stage: similarity index remained positive and relative transmission speed decreased by 11 %). The neurophysiological mechanism of drug interaction was further elucidated, which may provide the guidance for the optimal timing of drug administration. Following the further extension of biosensor longevity and the expansion of synchronous multidimensional parameter detection, including impedance and electrochemistry, it is anticipated that this will become a novel platform for the preclinical evaluation and screening of AD drugs.