Heart disease is the leading cause of death in the world. Finding future therapeutics for heart disease requires the development of mature 3D engineered human cardiac tissues that can serve as reliable models for biological studies and drug development. The ability to measure and stimulate cardiac action potentials (APs) is key to the development of these 3D tissue models.
Optical measurement and stimulation methods offer an enticing solution to longstanding tissue development testbed needs. However, existing optical measurement methods have relied on toxic voltage dyes and motion inhibiting drugs, and existing optical stimulation methods have mainly focused on optogenetic modification techniques.
In this dissertation, I present two related optical systems built for 3D engineered human cardiac microtissues, organized into two chapters: 1) a dual-mode voltage and contraction imaging optical microscope for tracking action potential metrics with fluorescent genetically encoded voltage indicator Archon1, and 2) an all optical cardiac stimulation system for unmodified engineered human cardiac micro-tissues with red and blue laser pulse options. These systems offer cardiac researchers less invasive optical solutions for cardiac action potential visualization and pacing: the microscope system allows direct action potential measurements without the use of toxic dyes, and the stimulation system allows ex-vivo pacing without any modification to the sample, genetic or otherwise. I will discuss the system design motivations, challenges, results, and mechanisms of this work.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/43722 |
| Date | 26 January 2022 |
| Creators | Sun, Jingyi (Jenny) |
| Contributors | Mertz, Jerome C. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
| Rights | Attribution 4.0 International, http://creativecommons.org/licenses/by/4.0/ |
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