OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology
We present a simple low-cost system for comprehensive functional characterization of cardiac function under spontaneous and paced conditions, in standard 96 and 384-well plates. This full-plate actuator/imager, OptoDyCE-plate, uses optogenetic stimulation and optical readouts of voltage and calcium...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-12-01
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| Series: | Journal of Molecular and Cellular Cardiology Plus |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772976123000247 |
| _version_ | 1797342074714980352 |
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| author | Yuli W. Heinson Julie L. Han Emilia Entcheva |
| author_facet | Yuli W. Heinson Julie L. Han Emilia Entcheva |
| author_sort | Yuli W. Heinson |
| collection | DOAJ |
| description | We present a simple low-cost system for comprehensive functional characterization of cardiac function under spontaneous and paced conditions, in standard 96 and 384-well plates. This full-plate actuator/imager, OptoDyCE-plate, uses optogenetic stimulation and optical readouts of voltage and calcium (parallel recordings from up to 100 wells in 384-well plates are demonstrated). The system is validated with syncytia of human induced pluripotent stem cell derived cardiomyocytes, iPSC-CMs, grown as monolayers, or in quasi-3D isotropic and anisotropic constructs using electrospun matrices, in 96 and 384-well format. Genetic modifications, e.g. interference CRISPR (CRISPRi), and nine compounds of acute and chronic action were tested, including five histone deacetylase inhibitors (HDACis). Their effects on voltage and calcium were compared across growth conditions and pacing rates. We also demonstrated optogenetic point pacing via cell spheroids to study conduction in 96-well format, as well as temporal multiplexing to register voltage and calcium simultaneously on a single camera. Opto-DyCE-plate showed excellent performance even in the small samples in 384-well plates. Anisotropic structured constructs may provide some benefits in drug testing, although drug responses were consistent across tested configurations. Differential voltage vs. calcium responses were seen for some drugs, especially for non-traditional modulators of cardiac function, e.g. HDACi, and pacing rate was a powerful modulator of drug response, highlighting the need for comprehensive multiparametric assessment, as offered by OptoDyCE-plate. Increasing throughput and speed and reducing cost of screening can help stratify potential compounds early in the drug development process and accelerate the development of safer drugs. |
| first_indexed | 2024-03-08T10:28:09Z |
| format | Article |
| id | doaj.art-03eba7659e964b38a91f5493fe2c6727 |
| institution | Directory Open Access Journal |
| issn | 2772-9761 |
| language | English |
| last_indexed | 2024-03-08T10:28:09Z |
| publishDate | 2023-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Molecular and Cellular Cardiology Plus |
| spelling | doaj.art-03eba7659e964b38a91f5493fe2c67272024-01-27T07:02:51ZengElsevierJournal of Molecular and Cellular Cardiology Plus2772-97612023-12-016100054OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiologyYuli W. Heinson0Julie L. Han1Emilia Entcheva2Department of Biomedical Engineering, The George Washington University, Washington, DC 20052, United States of AmericaDepartment of Biomedical Engineering, The George Washington University, Washington, DC 20052, United States of AmericaCorresponding author.; Department of Biomedical Engineering, The George Washington University, Washington, DC 20052, United States of AmericaWe present a simple low-cost system for comprehensive functional characterization of cardiac function under spontaneous and paced conditions, in standard 96 and 384-well plates. This full-plate actuator/imager, OptoDyCE-plate, uses optogenetic stimulation and optical readouts of voltage and calcium (parallel recordings from up to 100 wells in 384-well plates are demonstrated). The system is validated with syncytia of human induced pluripotent stem cell derived cardiomyocytes, iPSC-CMs, grown as monolayers, or in quasi-3D isotropic and anisotropic constructs using electrospun matrices, in 96 and 384-well format. Genetic modifications, e.g. interference CRISPR (CRISPRi), and nine compounds of acute and chronic action were tested, including five histone deacetylase inhibitors (HDACis). Their effects on voltage and calcium were compared across growth conditions and pacing rates. We also demonstrated optogenetic point pacing via cell spheroids to study conduction in 96-well format, as well as temporal multiplexing to register voltage and calcium simultaneously on a single camera. Opto-DyCE-plate showed excellent performance even in the small samples in 384-well plates. Anisotropic structured constructs may provide some benefits in drug testing, although drug responses were consistent across tested configurations. Differential voltage vs. calcium responses were seen for some drugs, especially for non-traditional modulators of cardiac function, e.g. HDACi, and pacing rate was a powerful modulator of drug response, highlighting the need for comprehensive multiparametric assessment, as offered by OptoDyCE-plate. Increasing throughput and speed and reducing cost of screening can help stratify potential compounds early in the drug development process and accelerate the development of safer drugs.http://www.sciencedirect.com/science/article/pii/S2772976123000247High-throughputAll-optical electrophysiologyOptogeneticsCardiotoxicityHuman iPSC-CMsDrug testing |
| spellingShingle | Yuli W. Heinson Julie L. Han Emilia Entcheva OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology Journal of Molecular and Cellular Cardiology Plus High-throughput All-optical electrophysiology Optogenetics Cardiotoxicity Human iPSC-CMs Drug testing |
| title | OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology |
| title_full | OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology |
| title_fullStr | OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology |
| title_full_unstemmed | OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology |
| title_short | OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology |
| title_sort | optodyce plate as an affordable high throughput imager for all optical cardiac electrophysiology |
| topic | High-throughput All-optical electrophysiology Optogenetics Cardiotoxicity Human iPSC-CMs Drug testing |
| url | http://www.sciencedirect.com/science/article/pii/S2772976123000247 |
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