Biomedical Engineering Reference
In-Depth Information
applied.to.the.substrate,.thereby.controlling.the.amount.of.cell-adhesive.proteins.acces-
sible.to.the.cells..Through.in.situ.adjustment.of.crack.widths,.morphology.of.cells.could.
be.reversibly.manipulated.
12.4 MicrofluidicSystemsforControllingCell-SolubleFactorInteractions
Microluidic.systems.play.a.key.role.in.cell-related.studies.since.they.consume.small.quan-
tities.of.samples.and.provide.a.rapid.analysis.in.a.high-throughput.manner.within.small.
channels.that.are.typically.in.the.range.of.10-100.µm.
56
.They.offer.several.advantages,.such.
as.reduced.analysis.time,.lower.sample.volume,.and.ability.to.run.multiple.assays.on.a.sin-
gle.device.
57,58
.With.the.advent.of.microluidic.systems,.cell.research.has.entered.into.a.new.
era.in.which.the.soluble.factors.can.be.controlled.within.microluidic.networks.to.generate.
sophisticated.conditions,.as.well.as.handle.cellular.molecules.precisely.for.transportation.
of.cells.to.the.desired.locations..Soluble.factors,.such.as.growth.factors,.are.proteins.that.
bind. to. receptors. on. the. cell. surface. and. activate. speciic. series. of. cellular. mechanisms,.
leading.to.events.like.cellular.proliferation.or.differentiation..Based.on.the.ability.to.con-
trol.cell.behavior,.effective.usage.of.growth.factors.has.been.investigated.for.directing.the.
lineage-speciic. differentiation. of. ESCs. using. microluidic. systems.. For. example,. activin.
A. was. shown. to. mediate. dorsoanterior. mesoderm. differentiation,. while. bone. morpho-
genic.protein.4.(BMP-4).was.shown.to.mediate.formation.of.hematopoietic.cells.
59-61
.These.
beneits.have.accelerated.the.application.of.microluidic.systems.to.investigate.cell-soluble.
factor.interactions.
12.4.1 Microfluidic Techniques for Cell Manipulation
Microluidic-based.cell.manipulation.approaches.have.generally.focused.on.how.to.handle.
a.single.cell.or.a.few.cells.inside.microluidic.systems.where.magnetic,.optical,.electrical,.or.
mechanical.forces.are.employed..We.briely.summarize.the.description.of.each.manipula-
tion.method.
Manipulation. using. magnetic. forces. generally. utilizes. magnetic. particles. to. identify.
speciic.cells..The.size.of.the.magnetic.particles.is.10-100.nm,.so.that.it.is.possible.to.uptake.
the.magnetic.particles.into.cells.with.little.effect.on.cell.function.and.viability..Lee.et.al..
implemented.an.embedded.8.×.8.microcoil.array.for.the.generation.of.magnetic.forces.in.
order.to.control.the.location.of.a.single.cell.on.the.microcoil.surface.
62
.Using.the.magnetic.
force.via.magnetic.particles.is.a.noninvasive.method.to.control.cells.inside.microluidics,.
but.the.development.of.a.new.conjugating.method.of.particles.into.ligands.and.the.simple.
integration.of.magnetic.force.generators.with.microluidics.remain.a.challenge.
Optical.tweezers,.due.to.an.electric.ield.gradient.around.a.focal.point.of.laser.light,.are.
commonly. used. in. cell. manipulation. since. they. are. easily. combined. with. microluidics.
systems.and.are.noncontact.methods..Live.mammalian.cells.are.successfully.sorted.using.
the. optical. method. within. a. short. time. (2-4. ms).
63
. Though. this. optical. method. requires.
only. transparent. windows. to. allow. light. passing. through. a. chip,. its. applications. in. cell.
manipulation.have.limitations.due.to.the.external.complex.optical.setups.
Dielectrophoresis.(DEP).is.a.popular.form.of.electric.force.application.in.microluidic.sys-
tems..DEP.can.easily.separate.cells.based.on.electrical.properties.in.electric.gradients.based.
on.a.principle.similar.to.optical.tweezers..Use.of.this.technique.inside.a.photopatternable.
