Biomaterials for MEMS

106 M. C. W. Chen and K. C. Cheung

Figure 5.14. (left) The shielded junction employed to generate alginate microspheres.

Aqueous sodium alginate mixed with CaCO3 and cells is introduced into the central

channel (A). Sunflower oil mixed with acetic acid is supplied to the outermost channels (C).

Sunflower oil is supplied to the intermediate channels (B) to act as a shield preventing the

alginate solution from coming into contact with the acidified oil flow. Between channels

B and A the two oils flow in a laminar fashion, with minimal diffusion of H+ into the

protective sunflower oil. After droplet formation at the junction, H+ diffuses into the

alginate droplet, thus liberating Ca2+ from CaCO3, which causes gelation of the alginate.

(right) Light microscope image of encapsulated PC12 cells, showing small cell clumps

present after encapsulation.

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U-2 OS cell lines.

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A droplet-based microfluidic system has also been used to form

alginate beads with entrapped breast tumor cells. The alginate environment per-

mitted cell proliferation and the formation of multicellular spheroids. The dose-

dependent response of the tumor spheroids to doxorubicin, and anticancer drug,

showed multicellular resistance compared to conventional monolayer culture.

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5.4.4 Other Configurations

A photopolymerizable polyethylene glycol (PEG) was used in combination with

dielectrophoresis (DEP) to trap cells in controlled, reproducible organizations.

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The ability to pattern cell clusters with varying size and spacing showed that

microscale organization and tissue architecture can affect cell behavior.

A combination of micropillars and gel encapsulation has been used in a

3-D perfusion system

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by Toh et al. In this work, the cells were immobilized

using the micropillar array, and then the cells were stabilized by a coacervated

methylated collagen/HEMA-MMA-MAA terpolymer. Their work has also used

polyethyleneimine-hydrazide as an inter-cellular linker, instead of the coacervated

hydrogel, to created a “gel-free” system.

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Soft lithography and replica molding has been used to cast 3-D gel objects from

collagen, Matrigel, and agarose.

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The cell densities in the gel modules ranged

from 10

8

–10

9

cells/cm

3

, which approaches the density in tissues. The gel objects

had lateral dimensions from 40 to 1000 μm.

On-chip gelation of NiPAAm has been achieved using microheaters to

encapsulate single cells which have been positioned using optical tweezers.

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Since

NiPAAm is a thermoreversible gel, the entrapped cell can be released by turning

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