High-density microelectrode array in CMOS technology applied to acute brain slice recordings and to gene-function studies

摘要

Microfabrication techniques and, in particular, CMOS technology are very powerful tools to devise bioelectronic and multielectrode microsystems. CMOS-based, fully integrated microelectrode arrays for bidirectional communication (stimulation and recording) with electrogenic cells are presented. These complex microsystems with integrated filter and amplification stages feature a high electrode density (3'150 electrodes per mm2) as well as low noise levels (3-7 muVrms) in the recorded signals and are capable of monitoring relevant electrophysiological responses of cells to electrical stimuli or to pharmacological agents with prospective applications in the fields of neuroscience or pharmascreening. Results from two exemplary applications are shown. In the first one, the system was used to record the electrical activity of cardiomyocytes. To modulate their electrogenic properties lentivirus-derived particles were selected to regulate the bone morphogenetic protein-2 gene expression. This provides a tool for gene-function studies and for the discovery and preclinical evaluation of novel genes with potential therapeutic effects. In the second application acute sagittal cerebellar slices have been used to assess the performance of the device and to demonstrate its potential for application in the field of neuroscience. Subcellular resolution could be demonstrated and spike sorting allowed for analysing the measured action potentials from single neurons.