Biomedical Engineering Reference
In-Depth Information
In vivo - oviduct
a
c
Uterine horn
Oviduct
Cervix
Site of fertilization
Embryo
In vitro
- microchannel
b
d
Inlet well and funnel
Outlet and luer
PDMS
Embryo
Glass
Drawings not to scale
FIGURE 5.60
A.biomimetic.device.for.in.vitro.fertilization..(From.Sherrie.G..Clark,.Kathyrn.Haubert,.
David.J..Beebe,.C..Edward.Ferguson,.and.Matthew.B..Wheeler,.“Reduction.of.polyspermic.penetra-
tion.using.biomimetic.microluidic.technology.during.in.vitro.fertilization,”.
Lab Chip
.5,.1229-1232,.
2005..Reproduced.with.permission.from.The.Royal.Society.of.Chemistry.)
stream and go into the laminar stream that leads to the bottom outlet, whereas nonmotile sperm
necessarily continue straight to the top outlet.
he penetration of in vitro-fertilized oocytes by more than one sperm (“polyspermy”) results
in unviable embryos and has haunted animal in vitro fertilization eforts for many years. In
vivo, the oocyte is “parked” at the ampullary-isthmic junction (the site of fertilization) and
the oviduct acts as a reservoir with a narrowing or “gate,” which guides the sperm to low to
the junction (
Figure 5.60a
). A team led by Matthew Wheeler from the University of Illinois at
Urbana-Champaign and David Beebe from the University of Wisconsin at Madison designed
in 2005 a biomimetic microluidic device featuring a microchannel constriction (
Figure 5.60b
)
that allows for immobilizing pig embryos (
Figure 5.60c
and
d
) and demonstrated an increase in
monospermy from approximately 22% (the controls, fertilized with the traditional “microdrop”
technique) to approximately 55% or 64%, depending on whether 10 or 15 oocytes were present in
the microchannel, respectively. here is additional evidence that this “biomimetic” efect is real,
because separate results with mouse embryos also demonstrated that embryonic development of
mouse embryos to the blastocyst stage was enhanced (exhibited a faster rate of cleavage, produc-
ing ~28%-24% more blastocysts) and showed a 2- to 3-fold reduction in degenerated embryos by
96 hours of culture compared with control microdrop cultures (the numbers varied depending
on whether the microchannels were constructed in silicon or PDMS).
5.11 Whole Animal Testing
he roundworm
Caenorhabditis elegans
is an approximately 1-mm-long transparent nematode
that has been widely used as a model organism for several decades now. he lineage of every cell
is known, as well as the connectivity and position of every neuron in its 302-neuron nervous sys-
tem. Seeing that it conveniently its in microchannels, in 2004, Cornelia Bargmann's laboratory at
Rockefeller University started using microluidics to study
C. elegans
behavior (see Section 6.5.5).
Recently, the laboratories of Nikos Chronis (who trained in the Bargmann laboratory) at the
University of Michigan and of Fatih Yanik at MIT have incorporated PDMS microactuator tech-
nology to immobilize the worms at high throughput (a PDMS membrane pushes the worm down),
