A Semi-Automated MEA Spike sorting (SAMS) method for high throughput assessment of cultured neurons

Neurons derived from human pluripotent stem cells (hPSCs) are valuable models for studying brain development and developing therapies for brain disorders. Evaluating human-derived neurons requires assessing their electrical activity, which can be achieved using multi-electrode arrays (MEAs) for extracellular recordings. Because each electrode channel generally detects activity from multiple neurons, resolving the activity of single neurons requires a process called spike sorting. However, currently available spike sorting methods are not optimized for the analysis of hPSC-derived neurons, and require complex workflows and time-consuming manual intervention. Here, we introduce a S emi- A utomated M EA S pike sorting software (SAMS) designed specifically for low-density MEA recordings of cultured neurons. SAMS outperforms commercially available automated spike sorting algorithms in terms of accuracy and greatly reduces computational and human processing time. By providing an accessible, efficient, and integrated platform for spike sorting, SAMS enhances the resolution and utility of MEA in disease modeling and drug development using human-derived neurons.