Microfluidics - Introduction to BioMEMS - page 186

Dispensing
pin

a c

Dextran
(M.W. 500,000)

PEG (M.W. 8,000)

Plasmid
DNA

1 mm eGFP

Dextran-FITC conjugate

dsRED

0 min 60 min 120 min 180 min 240 min

b

Lipofectamine
2000

700 µm

500 µm

FIGURE 3.84 Local. delivery. of. luids. onto. cells. using. a. two-phase. system.. (From. H.. Tavana,. A..
Jovic,. B.. Mosadegh,. Q.. Y.. Lee,. X.. Liu,. K.. E.. Luker,. G.. D.. Luker,. S.. J.. Weiss,. and. S.. Takayama,.
“Nanolitre.liquid.patterning.in.aqueous.environments.for.spatially.deined.reagent.delivery.to.mam-
malian.cells,”. Nat. Mater. .8,.736-741,.2009..Reprinted.with.permission.from.the.Nature.Publishing.
Group..Figure.contributed.by.Shu.Takayama.)

3.9.5 Gradients Delivered through a Semipermeable Barrier
We note that most of the previous devices rely on low (and some on fast low) to generate gradi-
ents or dilutions. For some applications, in particular, those that include cells in the microchan-
nels, low itself is a concern. hus, there have been many eforts directed at developing gradient
generators capable of producing gradients with negligible low by interposing a semipermeable
barrier between the area containing cells and the channel delivering the low.

3.9.5.1 Gradient Generators that Incorporate Porous Membranes
One design option, irst proposed by Matthew DeLisa and colleagues at Cornell University in
2006, is to build the walls of the device in … nitrocellulose paper! (Of note, this article can
be considered the irst contribution to the ield of paper microluidics.) his is a clever option
because the paper has a deined thickness (140 μm) and pore size (0.45 μm) and can be laser-cut
to deine 400-μm-wide channels. he device consists of three channels, capped with glass. he
gradient is created in the middle channel (where the cells reside) and the outer channels act as
the (ininite) source and the (ininite) sink for the chemoattractant. hus, the cells are never
exposed to low and are exposed to a linear gradient of chemoattractant ( Figure 3.85 ).
A diferent coniguration (in which difusion occurs in the vertical direction) has been pro-
posed by Michel Maharbiz and colleagues from the University of California at Berkeley. As
semipermeable barriers, they used thin polyester membranes (containing 0.4 μm pores, com-
mercially available as ilters) that allow for difusive but not convective transport. (his is
technically incorrect: there is always some amount of convection as long as there is a pressure
diferential, an inlet, and a path to an outlet; in the Maharbiz design, convection is minimized
by both the smallness of the pores, which maximizes resistance, and by the symmetry of the