An in vitro microfluidic culture device for peripheral neurotoxicity prediction at low concentration based on deep learning

Abstract

In this study, a microfluidic culture device was developed including related evaluation methods using deep learning for the purpose of constructing a rapid assessment platform for peripheral neuropathy caused by compounds. Primary rodent dorsal root ganglion was cultured in the microfluidic culture device that could separate the cell body and neurites, and the neurites morphological changes were analyzed by immunofluorescence images. Separated neurites successful culture in the microfluidic device for more than 1 month indicated that a series of test processes from culture to drug stimulation and fluorescence observation is possible. Additionally, cultured samples were treated with several anticancer drugs known to cause peripheral neurotoxicity (i.e., vincristine, oxaliplatin, and paclitaxel) and analyzed the neurites morphological changes by deep learning for image analysis. After training, artificial intelligence (AI) could identify neurite morphological changes caused by each compound and precisely predicted the toxicity positivity, even at low concentrations. For testing compounds, AI could also precisely detect toxicity negative and positive based on neurite images, even at low concentrations. Therefore, this microfluidic culture system is supposed to be useful for in vitro toxicity assessment.