Optical actuation and sensing methods were demonstrated by GW for high-throughput drug and cardiotoxicity screening. However, modification of target cells takes time, has variable yield and can cause potential interference with cell’s innate functional responses.
GW researchers manufactured “spark-cell” spheroids, used as a reagent that can be frozen, transported, and deployed on-site to confer optical pacing of cardiac cells. Since the spheroids are genetically engineered, one no longer needs to genetically modify the target cardiomyocytes of interest. Such spheroids can respond to electrical, optical, magnetic, and ultrasound/mechanical actuation. The spheroids are designed for easy robotic application, can be guided to desired location, can be assembled in higher-order structures, and can provide optimal level of stimulation to the target cardiomyocytes.
Figure: “Spark-cell” spheroids can be manufactured in a high-throughput (HT) format, and can be positioned onto hiPSC-cardiomyocytes, also grown in HT format. Shown is calcium response (trace and optical map) triggered by light engaging a deposited “spark-cell” spheroid.
Applications:
- High-throughput screening for cardiac toxicity
- Phenotyping iPSC-derived cardiomyocytes
- Tissue engineering and soft robotics
Advantages:
- Fast, cost-effective, high-throughput (>600 samples/hour)
- Allow precise optogenetic stimulation without genetic modification of cells of interest
- Allow all-optical electrophysiology - simultaneous voltage, calcium optical measurements
- Spheroids respond to electrical, optical, magnetic, and ultrasound signals
- Compatible with standard high-throughput plate format (96- or 384-well plates)
- Amenable to robotic handling for positioning and 3D tissue structure assembly
