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. 2021 Jan 18;12(1):96. doi: 10.3390/mi12010096

Table 1.

A comparison of MCS generation techniques.

Generation Methods Advantages Disadvantages References
Traditional generation methods Non-adhesive surface liquid covering (the microwell arrays method) Easy to operate
Low sheer stresses
High yield
Low cost
Labor intensive
Variation in MCSs size and shape
Inability to stimulate cell-ECM interactions
[7,21,22,23,24,25,26,27,28]
Hanging drop Easy to operate
Good size control
Low sheer stresses
Co-cultivation of multiple cells
Labor intensive
Low yield
Difficulties in mass production
Difficult to change the medium
Difficult to transfer the spheroid
[29,30,31,32]
Rotating flask Mass generation
Easy to operate
Long-term culture
Dynamic microenvironment
Co-cultivation of multiple cells
High sheer stresses
Variation in MCSs size and shape
Inconvenient to observe the generation process of the spheroid
Inability to stimulate cell-ECM interactions
[33]
External force Rapid generation
Good size control
Co-cultivation of multiple cells
Requiring professional equipment
The potential impact of external forces on cells is unknown
[10,34,35,36,37,38,39]
Biomaterials (scaffolds) and microfluidic technology Hydrogel (scaffold, cell sheets) Natural polymers Realistic microenvironment
High yield
Good size control
Low sheer stresses
Labor saving
Aggregates of different shapes can be generated
Co-cultivation of multiple cells
Requiring professional equipment
Higher requirements for operation
Higher cost
[40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74]
Synthetic polymers [75,76,77,78,79,80,81,82,83,84,85]
Microfluidic Emulsion technology Realistic microenvironment
High yield
Long-term culture
Good size control
Low sheer stresses
High-throughput analysis
Labor saving
Dynamic microenvironment
Generate aggregates of different shapes
Co-cultivation of multiple cells
Low reagent consumptionLow cell usage
Requiring professional equipment
Higher requirements for operation
Higher cost
[3,86,87,88,89,90,91,92,93]
Microwell and U-shaped microfluidic system [6,12,23,94,95,96,97,98,99,100]