Biomedical Engineering Reference
In-Depth Information
only.part.of.a.gene.can.enter.the.cell.before.the.cell.membrane.closes.in.MEP,.which.also.
happens.in.BEP.(Golzio.et.al..2002)..Thus,.genes.are.still.absorbed.by.endocytosis.after.the.
closure.of.the.cell.membrane..From.this.point,.MEP.doesn't.show.too.much.improvement,.
although.it.needs.a.much.smaller.electric.bias.than.BEP.
Not.until.most.recently.has.nanoelectroporation.(NEP).been.reported.in.the.Lee.group.
at. the. Ohio. State. University. (Boukany. et. al.. 2011).. Their. NEP. luidic. system. uses. the.
aforementioned. nanochannel-microwell. device,. fabricated. with. the. hybrid. fabrication.
technique. that. combines. top-down. (micromachining). and. bottom-up. (DNA. combining).
approaches.. NEP. has. a. totally. different. mechanism. from. BEP. or. MEP.. From. the. direct.
observation. of. the. migration. of. propidium. iodide. (PI). dye. into. electroporated. cells,. it. is.
found.that.the.PI.dye.is.directly.injected.into.the.cell.in.NEP,.instead.of.diffusing.through.
the. opened. cell. membrane. in. BEP. or. MEP.. There. are. two. advantages:. one. is. that. the.
transmembrane. potential. distribution. is. highly. localized. with. a. very. high. peak. value,.
thus. the. smallest. percentage. of. cell. membrane. is. broken. down;. the. other. is. that. genes.
have.been.largely.accelerated.in.nanochannels.due.to.the.huge.magnitude.of.the.electric.
ield. inside.. Thus,. it. seems. that. most. genes. are. quickly. injected. into. the. cell,. not. slowly.
absorbed.by.endocytosis..From.this.point,.NEP.is.more.like.the.technique.of.the.gene.gun..
Fundamental.study.of.NEP.is.just.beginning;.however,.it.will.deinitely.help.us.to.better.
understand.electroporation.at.the.molecular.and.cellular.levels.
18.5 Conclusions and Perspectives
In. summary,. we. revisit. some. important. transport. phenomena. and. major. driving. forces.
in.nanoluidics,.which.have.already.demonstrated.the.ability.to.control.the.dynamics.of.
nanoparticles.and.biomolecules..We.mainly.focus.on.EP.because.it.is.the.most.important.
phenomenon.in.nanoluidics.and.has.been.widely.used.in.many.biomedical.applications.
such. as. DNA. separation,. DNA. mapping,. and. electroporation.. Multiphase. phenomena.
are.also.important.since.they.can.be.used.to.manipulate.nanoparticles.and.biomolecules,.
especially.in.DNA.combining.
Before. ending. this. chapter,. we. would. like. to. propose. some. possible. future. directions.
for. nanoluidics-based. biomedical. applications.. First,. a. more. eficient. nanoluidic. device.
for.biomolecule.separation.should.be.the.miniaturization.of.the.current.Brownian.ratchet.
or.DNA.prism,.since.either.can.produce.a.spatial.separation,.which.is.the.most.powerful.
and.eficient.separation.technique.for.biomolecules..The.optimal.design.of.a.nanoscaled.
Brownian.ratchet.or.DNA.prism,.however,.might.need.the.help.of.numerical.simulations.
on.electric.ield.distribution.and.dynamics.of.biomolecules.
Second,. low-cost. and. high-throughput. DNA. mapping. might. be. achieved. using. the.
nanoluidics-based.DLA.method.or.nanopore.mapping.technique..These.two.ultrafast.and.
low-cost.techniques.simplify.the.procedure.of.DNA.mapping.and.are.continuous.in.pro-
cess.. Fundamental. understandings. of. biomolecule. behaviors. in. these. devices,. however,.
are.still.lacking.and.need.to.be.carried.out.for.design.and.optimization.purposes.
Third,. drug. and. gene. delivery. using. nanoluidics. are. very. promising.. Hindered. dif-
fusion. and. electroporation. using. nanostructures. are. two. techniques. mentioned. in. this.
chapter,. although. there. are. many. other. nanoluidics-based. methods. for. drug. and. gene.
delivery.. Future.work.of.drug.and.gene.delivery. shall.focus.on.the.biological.responses.
at.cellular.and.tissue.levels.for.better.understanding.of.the.mechanisms..This.would.help.
