Biomedical Engineering Reference
In-Depth Information
Maynard,.n.d.;.Krsko.et.al.,.2003;.Lussi.et.al.,.2005;.Nicolau.et.al.,.1999;.Reis.et.al.,.2010;.
Rundqvist.et.al.,.2006,.2007;.Saaem.et.al.,.2007;.Senaratne.et.al.,.2006;.Zhang.et.al.,.2004a,b)..
As.the.references.show,.there.is.a.great.diversity.of.materials,.approaches,.and.objectives.
for.functionalized.patterning..The.objective.frequently.consists.of.initiating.a.site-selective.
chemical.binding.for.anchoring.everything.from.amino.acids.to.cells..In.nanoelectronics,.
lithographic. ilms. called. resists. are. organic. polymers. that. are. cast. in. a. solvent. and. spin.
coated. onto. the. underlying. substrate.. This. is. followed. by. a. baking. step. to. drive. off. the.
solvent.. During. exposure. to. appropriate. radiation. (photons. or. charged. particles),. the.
polymer. either. responds. by. cross-linking. (negative. tone). or. scission. (positive. tone)..
The. exposure. process. thereby. induces. a. differential. solubility. between. the. exposed. and.
unexposed.regions.such.that.immersion.of.the.substrate.in.a.developer.(solvent).selectively.
removes.the.more.soluble.component.and.leaves.behind.a.masking.layer.that.can.be.used.
for.further.processing..One.way.to.achieve.functionalized.patterning.is.to.use.this.masking.
layer. to. deposit. bioactive. materials. selectively. at. designated. locations. on. the. substrate..
Removal. of. the. masking. layer. can. carry. the. unwanted. bioactive. materials. away.. One.
challenge.here.is.that.a.solvent.strong.enough.to.remove.the.unwanted.resist.frequently.
dissolves.the.biomolecules.as.well.
A.more.common.approach.in.biological.applications.is.to.coat.the.substrate.with.a.self-
assembled.monolayer.and.use.the.exposure.process.to.either.induce.or.inhibit.the.desired.
functionality..As.these.materials.are.not.standardized.within.the.lithographic.community,.
it. is. often. necessary. to. undertake. some. basic. characterization. studies. to. determine. the.
appropriate. exposure. conditions.. For. electron. beam. lithography. (EBL),. one. of. the. more.
important.factors.to.keep.in.mind.is.that.the.exposure.will.occur.under.conditions.of.a.high.
vacuum.. Any. substrate. and. material. combinations. intended. for. exposure. by. EBL. must.
exhibit.low.outgassing.properties.and.be.able.to.tolerate.vacuum.without.adverse.effects..
The.ability.of.a.material.to.coat.the.substrate.uniformly.is.also.important..Areas.with.voids.
or.contamination.must.be.kept.small.relative.to.the.features.to.be.patterned.or.the.integrity.
of.the.pattern.will.be.compromised.
For. resist. material,. a. dose. is. deined. such. that. for. a. given. dose,. the. conversion. of. the.
exposed.material.to.a.new.solubility.state.is.100%..By.performing.a.series.of.test.exposures.
over. a. range. of. doses. that. are. subsequently. exposed. to. a. developer,. one. may. obtain. a.
“contrast. curve”. that. plots. residual. thickness. versus. dose.. When. the. objective. is. not. to.
transform.solubility.but.rather.a.particular.functional.property.of.the.material,.a.similar.
strategy.may.be.employed.to.determine.the.appropriate.dose.
Topographical.patterning.(Hu.et.al.,.2010;.Prinz.et.al.,.2008;.Reis.et.al.,.2010).of.substrates.
is.another.active.area.of.biological.research.that.is.enabled.by.lithography..Conventional.
lithographic. means. are. employed. to. create. raised. or. recessed. structures. on. a. substrate,.
which. are. then. used. to. investigate. the. response. of. cellular. motility.. A. variation. of. this.
technique. combines. topographical. patterning. with. functionalization. for. multivariate.
experiments..The.high.resolution.of.EBL.enables.topographical.patterning.to.be.investigated.
at.nanoscale.dimensions.
Lithography. plays. important. supporting. roles. for. many. applications. relevant.
to. biological. research,. including. instrumentation,. micro-. and. nanoluidics,. DNA.
sequencing.and.manipulation,.cell.sorting,.lab.on.a.chip,.and.self-assembly.to.name.just.
a.few.(Stosch.et.al.,.2011;.Wang.et.al.,.2006;.Yanik.et.al.,.2003,.2010)..The.ield.is.too.large.
to.do.it.full.justice;.a.number.of.review.papers.(Curtis.and.Wilkinson,.1997;.Dittrich.and.
Manz,.2006;.Mendes.et.al.,.2007).may.guide.the.interested.reader.to.various.specialized.
subtopics.
