Artificial Multicellular Assemblies from Cells Interfaced with Polymers and Nanomaterials - Cell Surface Engineering: Fabrication of Functional Nanoshells - page 171

desired structures. An AC field can be used to achieve a quick controlled and
scalable multicellular assembly. The term dielectrophoresis(DEP) means the
interaction between the assembled particles due to an induced AC electric
field. 58,59 Shang et al., showed how DEP can be used in combination with
electrical detection methods to temporarily direct individual bacterial cells
across micrometer-sized electrode junctions. However, as the cells can only
be arranged temporarily by the AC field, a new cell-assembly method was
developed as the combination of physical manipulation (DEP) and biomo-
lecular recognition using biotin and avidin. 60 Avidin has multiple binding
sites for biotin and an extremely high binding constant. This allowed the
cells or the gold nanorods functionalized with biotin to be assembled with
the application of DEP between the electrodes functionalized with avidin
and when the AC filed was removed they remained in position because of the
adhesion produced by the biotin and avidin interaction. 60 An obvious
drawback of this process is that it is not easy to coat any living cells with
biotin. Small et al. 26 used DEP and a combination of hydrogel trapping and
polyelectrolyte-mediated binding to permanently ''arrest'' the position of
living yeast cells in long linear aggregates after the removal of the electric
field. The yeast cells were pretreated using PAH and carboxymethyl cellulose
(CMC), cationic and anionic polyelectrolytes respectively, by using the LbL
method. The gelation of the agarose solution trapped the cell assemblies
that were further treated with oppositely charged polyelectrolyte (PAH)
introduced electrophoretcially in the gel to permanently bind the cells in the
linear structure. The agarose gel matrix was then dissolved, which in turn
produced free-standing yeast cell strings that were locked in linear structures
(Figure 9.5g) when using any templates or scaffold structures. The viability of
the cells was confirmed using fluorescein diacetate solution (Figure 9.5h).
Gupta el al. 61,62 demonstrated the permanent assembly of cells by using
DEP and functionalized synthetic microparticles binding to the cells
through biospecific interactions. The chips were designed with a two co-
planar electrode system with the application of the electric field in one
direction resulted in the formation of live yeast cell chains, as shown in
Figure 9.5c. They illustrate that at low frequencies smaller particles are
captured in between the cell junctions by positive dielectrophoresis. By
using this effect to capture surface-functionalized colloidal particles they
demonstrated how permanent cell structures can be assembled on a chip.
On a chip with a four-electrode system the application of electric field in two
perpendicular directions resulted in the formation of a 2D ordered array of
cells, as illustrated in Figure 9.5d.

d n 8 y 4 n g | 2

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9.5 Assembly of Tissue Spheroids
Cellular spheroids are 3D cell-culture models that are being actively explored
for the reconstruction of organs and tissues by bioprinting methods. The
tissue spheroids can be produced using various processes in which con-
ditions are engineered so that cells tend to aggregate together, rather than