High throughput screening system for engineered cardiac tissues
Introduction: Three dimensional engineered cardiac tissues (3D ECTs) have become indispensable as in vitro models to assess drug cardiotoxicity, a leading cause of failure in pharmaceutical development. A current bottleneck is the relatively low throughput of assays that measure spontaneous contract...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1177688/full |
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| author | Marshall S. Ma Marshall S. Ma Subramanian Sundaram Lihua Lou Arvind Agarwal Christopher S. Chen Thomas G. Bifano Thomas G. Bifano |
| author_facet | Marshall S. Ma Marshall S. Ma Subramanian Sundaram Lihua Lou Arvind Agarwal Christopher S. Chen Thomas G. Bifano Thomas G. Bifano |
| author_sort | Marshall S. Ma |
| collection | DOAJ |
| description | Introduction: Three dimensional engineered cardiac tissues (3D ECTs) have become indispensable as in vitro models to assess drug cardiotoxicity, a leading cause of failure in pharmaceutical development. A current bottleneck is the relatively low throughput of assays that measure spontaneous contractile forces exerted by millimeter-scale ECTs typically recorded through precise optical measurement of deflection of the polymer scaffolds that support them. The required resolution and speed limit the field of view to at most a few ECTs at a time using conventional imaging.Methods: To balance the inherent tradeoff among imaging resolution, field of view and speed, an innovative mosaic imaging system was designed, built, and validated to sense contractile force of 3D ECTs seeded on a 96-well plate. Results: The system performance was validated through real-time, parallel contractile force monitoring for up to 3 weeks. Pilot drug testing was conducted using isoproterenol.Discussion: The described tool increases contractile force sensing throughput to 96 samples per measurement; significantly reduces cost, time and labor needed for preclinical cardiotoxicity assay using 3D ECT. More broadly, our mosaicking approach is a general way to scale up image-based screening in multi-well formats. |
| first_indexed | 2024-04-09T13:18:48Z |
| format | Article |
| id | doaj.art-50de4bfbaa7d43d29c4d57b9855af888 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-09T13:18:48Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-50de4bfbaa7d43d29c4d57b9855af8882023-05-11T11:23:02ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-05-011110.3389/fbioe.2023.11776881177688High throughput screening system for engineered cardiac tissuesMarshall S. Ma0Marshall S. Ma1Subramanian Sundaram2Lihua Lou3Arvind Agarwal4Christopher S. Chen5Thomas G. Bifano6Thomas G. Bifano7Mechanical Engineering, Boston University, Boston, MA, United StatesPhotonics Center, Boston University, Boston, MA, United StatesBiomedical Engineering, Boston University, Boston, MA, United StatesMechanical and Materials Engineering, Florida International University, Miami, FL, United StatesMechanical and Materials Engineering, Florida International University, Miami, FL, United StatesBiomedical Engineering, Boston University, Boston, MA, United StatesMechanical Engineering, Boston University, Boston, MA, United StatesPhotonics Center, Boston University, Boston, MA, United StatesIntroduction: Three dimensional engineered cardiac tissues (3D ECTs) have become indispensable as in vitro models to assess drug cardiotoxicity, a leading cause of failure in pharmaceutical development. A current bottleneck is the relatively low throughput of assays that measure spontaneous contractile forces exerted by millimeter-scale ECTs typically recorded through precise optical measurement of deflection of the polymer scaffolds that support them. The required resolution and speed limit the field of view to at most a few ECTs at a time using conventional imaging.Methods: To balance the inherent tradeoff among imaging resolution, field of view and speed, an innovative mosaic imaging system was designed, built, and validated to sense contractile force of 3D ECTs seeded on a 96-well plate. Results: The system performance was validated through real-time, parallel contractile force monitoring for up to 3 weeks. Pilot drug testing was conducted using isoproterenol.Discussion: The described tool increases contractile force sensing throughput to 96 samples per measurement; significantly reduces cost, time and labor needed for preclinical cardiotoxicity assay using 3D ECT. More broadly, our mosaicking approach is a general way to scale up image-based screening in multi-well formats.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1177688/fullhigh throughput imaging(HTI)engineered cardiac tissuecardiotoxicity screeningPDMSmicro manufacturing |
| spellingShingle | Marshall S. Ma Marshall S. Ma Subramanian Sundaram Lihua Lou Arvind Agarwal Christopher S. Chen Thomas G. Bifano Thomas G. Bifano High throughput screening system for engineered cardiac tissues Frontiers in Bioengineering and Biotechnology high throughput imaging(HTI) engineered cardiac tissue cardiotoxicity screening PDMS micro manufacturing |
| title | High throughput screening system for engineered cardiac tissues |
| title_full | High throughput screening system for engineered cardiac tissues |
| title_fullStr | High throughput screening system for engineered cardiac tissues |
| title_full_unstemmed | High throughput screening system for engineered cardiac tissues |
| title_short | High throughput screening system for engineered cardiac tissues |
| title_sort | high throughput screening system for engineered cardiac tissues |
| topic | high throughput imaging(HTI) engineered cardiac tissue cardiotoxicity screening PDMS micro manufacturing |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1177688/full |
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