Abstract
Details
Induced pluripotent stem cell (iPSC)-derived neurons show immense promise as a tool for in-vitro human disease modeling and pharmacological testing. However, synaptic maturation, especially the formation of dendritic spines, can be slow and limited in iPSC-derived neurons and may require long-term cultures or brain organoids. The accelerated iPSC differentiation achieved by transcription-factor (TF) based methods allows access to more mature and functional synapses in a shorter period. Elixirgen Scientific's rapid differentiation method, namely the Quick-Tissue™ technology, induces the conversion of human iPSCs to highly homogenous neurons in only 10 days. These neurons reach advanced synaptic maturation and spinogenesis in approximately 70 days, accompanied by increased electrical activity and a robust network formation. In this Application Note, we utilized high-density microelectrode arrays (HD-MEAs) to demonstrate how label-free measurements of electrical activities can characterize mature excitatory neurons through various functional readouts. We used the MaxTwo HD-MEA system from MaxWell Biosystems, which features an integrated chip with 26,400 electrodes per well, enabling high-resolution extracellular recordings of action potentials across different scales, ranging from cell population networks to single-cell and subcellular levels. This approach offers a powerful method for studying neuronal physiology and disease-induced phenotypes in vitro4. Combining mature iPSC-derived neurons with HD-MEA technology offers the potential to develop reliable models and assays highly relevant to human brain functions and cognitive disorders, thereby accelerating drug discovery and personalized therapeutic strategies.