Biomedical Engineering Reference
In-Depth Information
energy. to. get. out. of. the. trap.. Entropy. trapping. shows. a. new. size-dependent. separation.
mechanism.in.which.large.DNA.is.more.favored.in.gaining.higher.mobility..It.seems.that.
this.mechanism.might.also.contribute.to.the.separation.of.large.DNA.molecules.in.nano-
pillar.arrays.with.small.spacing.(Ogawa.et.al..2007).
Another.method.to.separate.DNA.molecules.or.segments.is.entropy.recoil.using.on-and-
off.pulsed.electric.ields.(Cabodi.et.al..2002;.Turner.et.al..2002)..In.entropy.recoil,.the.on-time.
of.the.electric.ield.is.adjusted.so.that.a.small-sized.DNA.can.totally.enter.the.nanostructure,.
while.the.majority.part.of.a.large.DNA.still.stays.outside.of.the.nanostructure..Because.of.
the.coninement.effect.of.the.nanostructure,.a.small.DNA.remains.in.the.nanostructure.
during. the. off-time. of. electric. ield.. However,. the. large. DNA. coils. back. due. to. the. net.
elastic.force.exerted.by.the.outside.segments..Thus,.after.several.on-and-off.cycles,.small.
DNAs.can.be.separated.from.large.DNAs..However,.entropy.coil.is.not.an.eficient.way.
to. separate. DNA. molecules. with. different. sizes. since. it. can. only. separate. short. DNA.
molecules. from. those. above. the. threshold. size,. which. is. mainly. determined. by. the. size.
of.the.nanostructure.and.is.not.highly.sensitive.to.the.strength.and.frequency.of.pulsed.
electric.ield.
By. creating. a. 2D. asymmetric. obstacle. array,. the. so-called. Brownian. ratchet. has. been.
used.to.separate.DNA.molecules.or.fragments.(Huang.et.al..2004)..This.technique.recti-
ies.the.lateral.Brownian.motion.of.DNAs.and.delects.their.trajectories.perpendicular.to.
the.applied.electric.ield..The.device.is.very.similar.to.the.bean.machine.or.plinko.board.
that.appeared.on.the.American.television.game.show.“The.Price.is.Right.”.Different.from.
artiicial. EP. that. uses. micro-. or. nanopillar. array,. which. is. a. 1D. separation. system. and.
DNAs. are. only. separated. in. one. direction,. the. Brownian. ratchet. can. spatially. separate.
DNAs. and. is. essentially. a. 2D. separation. method.. Currently,. the. obstacle. arrays. in. the.
Brownian. ratchet. are. in. microscale. and. the. miniaturization. to. nanoscale. has. not. been.
reported,.although.it.is.very.possible.
DNA.prism.is.another.eficient.and.fast.way.to.separate.long.DNA.molecules.from.short.
ones.that.uses.temporally.alternating.electric.ields.in.different.directions.and.magnitudes.
(Huang.et.al..2002)..The.device.still.uses.the.micropillar.array.mentioned.earlier,.but.the.
pulsed.electric.ields.alternatively.change.directions.and.strength..This.setup.of.the.electric.
ield.is.really.the.game-changer.and.enables.the.DNA.prism.to.produce.both.spatial.and.
temporal.separation.of.DNAs.
Finally,.DNA.separation.can.also.be.achieved.in.nanosphere.solutions.(Tabuchi.et.al..2004)..
Highly.packed.nanospheres.form.tiny.passages.for.DNA.molecules.to.electrophoretically.
migrate.through..The.interaction.between.DNA.molecules.and.closely.packed.nanospheres.
is. very. complicated. and. highly. dependent. on. the. DNA. size.. Its. separation. mechanism.
needs.to.consider.the.surface.forces.between.nanospheres.and.DNAs,.the.highly.distorted.
electric.ield.in.the.porous.medium.formed.by.packed.nanospheres,.and.the.collisions.of.
DNAs.with.nanospheres.
18.4.2 Nanofluidic DNA Mapping
DNA.sequencing.is.of.high.importance.in.medicine.and.health.care..Single-base.resolution.
sequencing. of. large. or. chromosome-type. DNA. molecules. is. really. complicated. and.
sometimes. unnecessary. since. we. might. be. more. interested. in. determining. individual.
genes,.which.contain.many.base.pairs..The.determination.of.gene.location.is.called.DNA.
mapping.. Its. traditional. approach. is. to. irst. cut. large. DNAs. into. many. small. fragments.
using.restriction.enzymes.or.via.shearing.with.mechanical.force,.and.then.to.map.these.
DNA.fragments.using.gel.or.capillary.EP..This.approach,.however,.is.time-consuming.and.
