Biomedical Engineering Reference
In-Depth Information
Control
channel
Scaffold
channel
Cell
channel
Scaffold
channel
Condition
channel
a
Scaffold
Scaffold
Diffusion
0.6 mm
Control
media
Control
media
+ cells
Condition
media
Scaffold
Scaffold
1.3 mm
1 mm
*Channel height
= 0.12 mm
b
0.2 % collagen
pH 7.4
Gradient
FIGURE 3.91
Gradient. generator. incorporating. collagen. gels. as. diffusional. barriers.. (From. Seok.
Chung,.Ryo.Sudo,.Peter.J..Mack,.Chen-Rei.Wan,.Vernella.Vickerman,.and.Roger.D..Kamm,.“Cell.
migration.into.scaffolds.under.co-culture.conditions.in.a.microluidic.platform,”.
Lab Chip
.9,.269-
275,.2009..Reproduced.with.permission.from.The.Royal.Society.of.Chemistry.)
to it. However, the control experiment is usually done with a diferent set of cells, not with the
same set of cells because there is no way to expose the cells to two gradients simultaneously (to see
which one the cells prefer). Roger Kamm's group at MIT has demonstrated a design that simul-
taneously presents the cells with both the control condition and the gradient condition—and the
cells choose (
Figure 3.91
). he clever design also takes advantage of the fact that the hydrogel pre-
cursor is actually a viscous solution, so that when it is introduced in a channel that has small side-
openings that connect to other channels, the hydrogel precursor will not spill into those other
channels—this point is crucial because the small side-openings are the same openings through
which the gradient is later established and cells are allowed to migrate. he channel that contains
the cells is in the center and can be illed with cell culture medium or ECM hydrogel (poten-
tially allowing for 3-D cell migration experiments). Ultimately, this device could beneit from all
the automation technology that already exists for PDMS (microvalves, micropumps, etc.).
Hydrogels are inexpensive to produce in a research setting but are not adequate as commer-
cial devices—they are not easily assembled nor manufactured in large quantities. In addition,
they cannot be produced thin, so they are not suitable for fast-varying gradients or, equivalently,
for steep gradients of small molecules—the hydrogel “blurs” them.
3.10 Combinatorial Mixers
In many applications, it is desirable to produce not only several titrations of a given compound
but also
mixtures of two or more
compounds, including their titrations. he author's laboratory
at the University of Washington in Seattle has devised a microluidic mixer design that produces
all the mixture combinations of four dilutions of (two) input compounds and delivers the six-
teen mixture combinations in separate outlet microchannels (
Figure 3.92
). he device features
four diferent low levels made by stacking nine laser-cut Mylar laminates. he luidic network
has a symmetric design that guarantees that the low rates are nearly identical at all the outlets.
Such systems should ind uses in cancer and toxicology screening.
