Biomaterials for MEMS

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

Figure 5.10. (A) Optical micrograph showing six microchemostats that operate in parallel

on a single chip. Various inputs have been loaded with food dyes to visualize channels

and sub-elements of the microchemostats. The coin is 18 mm in diameter. (B) Optical

micrograph showing a single microchemostat and its main components. Scale bar, 2 mm.

(C) Schematic diagram of a microchemostat in continuous circulation mode. Elements such

as the growth loop with individually addressable connected segments, the peristaltic pump,

supply channels, and input/output ports are labeled. (D) Isolation of a segment from the

rest of the growth chamber during cleaning and dilution mode. A lysis buffer (indicated in

red) is introduced into the chip through the lysis buffer port. Integrated microvalves direct

the buffer through the segment, flushing out cells, including those adhering to chamber

walls. The segment is then rinsed with fresh sterile medium and reunited with the rest of

the growth chamber.

46

For color reference, see page 263.

tumor cells, permitting tumor spheroid formation and anticancer drug testing.

67

5.4.2 Microfluidic Agarose Cell Culture

In an alternative configuration, the microfluidic channel itself can be made of

hydrogel in which the cells have been seeded. Ling et al. have molded microfluidic

channels made of agarose seeded with cells

68

(Fig. 5.12). The mold master was

made using SU-8 patterned on a silicon wafer. Low gel-temperature agarose was

mixed with phosphate buffered saline and cooled to 70

◦

C, when it was loaded with

AML-12 hepatocytes. The mixture was poured onto the mold master and gelled.

A flat slab agarose was sealed onto the de-molded structure to created closed

microchannels. Culture medium was supplied using a syringe pump through the

microchannels. Although they were able to achieve uniform cell seeding, and good

SO13997_text.indd 110SO13997_text.indd 110 26/01/2011 3:50 PM26/01/2011 3:50 PM

Hydrogel-Based Microfluidic Cell Culture 103

Figure 5.11. Microchannel layout for on-chip formation of alginate layers with embedded

cells using laminar flows of alginate and Ca

2+

.

63

Figure 5.12. Schematic of the fabrication of agarose microfluidic devices with (right) and

without (left) embedded cells.

68

For color reference, see page 263.

SO13997_text.indd 111SO13997_text.indd 111 26/01/2011 3:50 PM26/01/2011 3:50 PM