Analyzing developing brain-on-chip cultures with the calima calcium imaging tool

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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.

Original languageEnglish
Article number412
Number of pages13
JournalMicromachines
Volume12
Issue number4
DOIs
Publication statusPublished - Apr 2021

Bibliographical note

Funding Information:
Acknowledgments: The authors wish to express their thanks to Fer Radstake for developing and maintaining CALIMA 1.0, and Martijn van Beurden and Wytse Wadman for sharing their insights regarding the points on which CALIMA 1.0 could be improved. We like to thank Sijia Xie to provide access to the raw data sets collected on primary rat cortical cells in the framework of RL’s European Research Council (ERC)—StG project under Grant Agreement No. 28028. Furthermore, we would like to thank Alex Bastiaens for performing the hiPSNC-cell culture and acquiring the CI TIFF-images used for dataset 2.

Funding Information:
This research was funded by the European Union?s Horizon 2020 research and innovation programme H2020-FETPROACT-2018-01 under Grant Agreement No. 824070 and the Eurostar?s MINDMAP project under Grant Agreement No. E113501.

Funding Information:
Funding: This research was funded by the European Union’s Horizon 2020 research and innovation programme H2020-FETPROACT-2018-01 under Grant Agreement No. 824070 and the Eurostar’s MINDMAP project under Grant Agreement No. E113501.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.

Keywords

  • Brain-on-chip culture
  • Calcium fluorescence imaging
  • Neuronal network
  • Software tool

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