Analyzing Developing Brain-On-Chip Cultures with the CALIMA Calcium Imaging Tool

Abstract

Brain-on-chip (BoC) models are tools for reproducing the native microenvironment of neurons, in order to study the (patho)physiology and drug-response of the brain. Recent developments in BoC techniques focus on steering neurons in their activity via microfabrication and via computer-steered feedback mechanisms. These cultures are often studied through calcium imaging (CI), a method for visualizing the cellular activity through infusing cells with a fluorescent dye. CAlciumImagingAnalyser 2.0 (CALIMA 2.0) is an updated version of a software tool that detects and analyzes fluorescent signals and correlates cellular activity to identify possible network formation in BoC cultures. Using three previous published data sets, it was demonstrated that CALIMA 2.0 can analyze large data sets of CI-data and interpret cell activity to help study the activity and maturity of BoC cultures. Last, an analysis of the processing speed shows that CALIMA 2.0 is sufficiently fast to process data sets with an acquisition rate up to 5 Hz in real-time on a medium-performance computer.

Vertebrates on a Chip: Noninvasive Electrical and Optical Mapping of Whole Brain Activity Associated with Pharmacological Treatments

“…The brain-wide connectivity among the selected ROIs can be analyzed by calculating the correlation coefficient matrix (Figure d), which showed that PTZ treatment not only increased the spike counts (Figure c), but also affected signal transmission in the animal’s brain by causing abnormal synchronization across brain networks . Specifically, brain-wide connectivity among the selected ROIs was analyzed by CALIMA . The tool facilitates the computation of cross-correlation between ROIs to generate functional connectivity maps (Figure e).…”

“…Brain-wide connectivity among the selected ROIs was analyzed by calculating the correlation coefficient matrix using CALIMA . The tool facilitates the computation of cross-correlation between ROIs to generate functional connectivity maps.…”

“…20 Specifically, brainwide connectivity among the selected ROIs was analyzed by CALIMA. 36 The tool facilitates the computation of crosscorrelation between ROIs to generate functional connectivity maps (Figure 5e). Functional connectivity was assessed across a range of minimum correlation factors, ranging from 0.0 to 1.0.…”

Current progress and challenges in the development of brain tissue models: How to grow up the changeable brain in vitro?

“…mitochondrial activity, calcium and cytoskeletal dynamics), molecular profiling of cells and extracellular fluids by means of transcriptomic, proteomic, metabolomic approaches in (patho)physiological conditions. 11 , 218 , 273 – 275 …”

Editorial for the Special Issue on Microfluidic Brain-on-a-Chip

“…Above all, we need systems and data harvesting techniques that provide us information of continuous variation of the cell dynamics. Raaijmakers et al [ 29 ] provide us, in this special issue, insights in software-driven labor reduction in live-cell calcium imaging applications for brain-on-chips. Additionally, the contribution by Forro et al [ 20 ] discusses the most recent developments of brain model read-outs utilizing electrical means.…”