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. 2023 Jan 18;8(4):3630–3649. doi: 10.1021/acsomega.2c06052

Table 2. Comparison of the Microfluidic-Based Methods for Spheroid Fabrication.

methods advantages limitations
droplet-based • create identical templates for spheroid formation • resulting empty droplets (no cell containment)
  • single, double, and triple encapsulation variations • insufficient nutrient supply
electrowetting • easy automation and integration • hard to design and fabricate these platforms
  • rapid analysis  
  • pump and valve-free operation  
microwell • simple to operate • cell loss and spheroid disruption during spheroid collection
  • controllable spheroid size  
microfluidic hanging drop • self-assembly due to gravity • high flow rate used to collect formed spheroids can damage spheroids
  • no cell adhesion observed on the surfaces • nonhomogeneous number of cells in each hanging drop
microstructures • reversible process enabling formation and collection of spheroids • applying high flow rate can affect the spheroid formation time and make cells escape
  • efficient cell trapping due to high cellular interaction  
acoustic • rapid spheroid formation enabling high cell viability • possible cell damage due to heating problems while using high-frequency acoustic fields
  • simple and versatile technology to fabricate complex spheroids patterns in mild conditions • complex fabrication processes while integrating acoustic wave generators on chip level
dielectrophoresis • fast cell manipulation • possible cell damage due to high electrical field
  • stable cell positioning • high conductivity of culture medium may result in low cellular interactions and induce cell damage