Biomedical Engineering Reference
In-Depth Information
surface. of. different. types. of. bones. in. air.. Xu. et. al.. (2003). demonstrated. microstructural.
characterization.of.bone.with.AFM;.this.group.was.able.to.exploit.the.high-resolution.capa-
bilities.of.AFM.to.compare.the.subtle.topographical.and.roughness.differences.between.
human.lamellar.bone.that.had.either.been.microtomed.or.mechanically.polished..Aside.
from.bone,.Lombardo.et.al..used.AFM.to.simultaneously.image.and.measure.the.visco-
elastic.properties.of.human.cornea.in.aqueous.solution.(Lombardo.et.al..2012)..Additional.
tissue.samples.that.have.been.characterized.with.AFM.include.skin.(Bhushan.2011),.teeth.
(Ma.et.al..2009),.and.human.ingernails.(Vaka.et.al..2011).
16.3.3 imaging the interior of Samples
One. major. limitation. of. AFM. for. biological. imaging. is. the. inability. to. transcend. the.
specimen. surface. to. capture. the. internal. features. of. a. sample.. In. recent. years,. several.
AFM-based. techniques. have. been. developed. and. applied. primarily. to. characterize. the.
magnetic,.conductive,.or.mechanically.excitable.properties.of.solid-state.materials..These.
same. techniques. are. now. being. adapted. to. detect. similar. properties. in. biological. speci-
mens.to.reveal.characteristics.not.only.on.the.surface.but.also.from.within.the.sample's.
interior.. Among. these. techniques. are. magnetic. force. microscopy. (MFM),. eddy. current.
microscopy.(EdCM),.ultrasonic-AFM.(UAFM),.scanning.near-ield.ultrasonic.holography.
(SNFUH),. and. mode-synthesizing. AFM. (MSAFM).. We. highlight. these. techniques. later.
and.describe.their.potentials.for.probing.the.subsurface.properties.of.biological.samples.
In.MFM,.an.AFM.probe.coated.with.a.magnetic.material.(usually.Co-Cr).is.used.to.detect.
long-range.magnetic.interactions.between.the.probe.and.the.magnetic.domains.within.a.
sample. (see. Figure. 16.2D).. The. magnetic. moment. of. the. MFM. probe. increases. (and. the.
spatial. resolution. decreases). proportionally. with. the. thickness. of. the. magnetic. coating..
MFM. is. routinely. used. in. the. semiconductor. industry. to. characterize. memory. devices.
(Zavaliche.et.al..2005;.Newman.et.al..2007)..The.synthetic.or.natural.magnetic.nanoparticles.
encountered.in.biological.applications,.however,.typically.have.a.single.magnetic.domain.
and. in. turn. a. (comparatively). weak,. superparamagnetic. moment. (see. Figure. 16.2E).. For.
MFM.to.serve.as.a.valuable.tool.for.magnetic.imaging.in.bionanotechnology,.a.signiicant.
improvement.in.MFM.force.sensitivity.must,.therefore,.be.achieved.without.compromising.
the. inherently. high. spatial. resolution. of. AFM.. Over. the. last. decade,. MFM. applications.
have. expanded. to. include. characterization. of. iron-containing. proteins. such. as. ferritin.
(Hsieh.et.al..2010),.bioconjugated.magnetic.nanoparticles.in.vitro.(Arakaki.et.al..2004),.and.
magnetic.crystals.present.inside.small.organisms.(Proksch.et.al..1995)..A.comprehensive.
overview. of. the. MFM. technique. (Hartmann. 1999). and. its. development. for. life. sciences.
(Agarwal.2009).are.described.in.the.cited.literature.
EdCM. is. another. AFM-based. technique. that. can. map. the. internal. characteristics. of. a.
sample..In.principal,.eddy.currents.are.produced.and.can.be.detected.when.a.time-varying.
magnetic. ield. interacts. with. a. conductor;. a. macroscaled. version. of. this. detection. tech-
nique. is. well. established. for. studying. subtle. subsurface. laws. in. electrically. conductive.
materials.(Wincheski.et.al..1994)..Recently,.the.combination.of.the.fundamental.principles.
of.eddy.current.detection.with.the.sensitive,.high-resolution.force.mapping.and.imaging.
characteristics.of.AFM.has.given.rise.to.EdCM.(Nalladega.et.al..2008)..EdCM.is.routinely.
used. for. detecting. submicron-sized. laws. in. different. types. of. metals. (Hoffmann. et. al..
1998;.Nalladega.et.al..2008),.but.has.yet.to.ind.applications.in.bionanotechnology..Because.
of.EdCM's.noncontact,.high.spatial.resolution,.and.picoNewton-sized.force.sensitivity,.it.is.
an.excellent.candidate.for.mapping.the.subsurface.properties.of.biological.specimen..The.
transition.of.EdCM.into.biological.imaging.will.require.a.careful.understanding.of.how.
