- 1 -
-
2002. 12
- 2 -
21 , (IT, BT, NT ),
,
( ) , ,
.
' '
,
. 21
, , , , ,
.
,
.
.
.
.
- 3 -
-
.
.
.
, .
(KISTI)
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.
-
.
, , , ,
, ,
,
.
2002. 12.
- 4 -
.
1
1.
.
.
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(2)
2.
.
.
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(2) ( )
(3)
(4)
(5) MEMS
- 5 -
2
1.
.
(1)
(2)
(3)
(4)
.
2.
.
.
3.
3
1.
.
.
2.
3.
< >
- 6 -
. (Nano Fluidics)
1
1.
2.
.
(1) DNA (DNA chip)
(2) (Protein chip)
(3) (Cell chip)
.
(1) (Nano-hardware)
. (Nano-wetware)
2
1.
.
(1)
(2)
(3)
(4)
(5)
(6)
(7)
.
(1) (Protein Patterning)
(2) (Nanoscale flow control)
(3) (Single Molecule Detection)
- 7 -
2.
.
.
(1) (flow cytometry)
(2) (lab-on-a-chip)
(3)
3.
3
1.
2.
.
.
.
3.
4.
5.
< >
- 8 -
.
1
1.
2.
2
1.
.
.
2. (Magnetic Drug Targeting)
.
.
3.
.
.
.
4. (hyperthermia)
.
.
5.
3
1.
.
.
2.
3.
- 9 -
.
/
/
- 10 -
1
1.
1965 Richard P. Feynman
(CalTech) 1959 "There's Plenty of Room at the bottom(
.)" .
,
.
21 , , ,
. 1980
(Scanning Tunneling Microscope : STM) (Atomic Force
Microscope : AFM)
.
- 11 -
, , ,
( ), ,
DNA , , ( ) .
,
.
21
.
Feynman
. .
, ,
.
.
1930 (nuclear revolution) 1960
(molecular revolution) .
, ,
.
30
, ,
.
- 12 -
.
(10-9 ) 35
,
(biomachines) .
(1) BC 400 ' ' ' (Atom)'
.
(2) 1905 1
.
(3) 1931 (Max Knoll). (Ernst Ruska) 1
.
(4) 1959 (Richard Feynman)
.
(5) 1968 (Alfred Y. Cho) (John Arthur)
.
- 13 -
(6) 1974 1
' ' .
(7) 1981 (Gerd Binnig) (Heinrich Roher)
(STM) .
(8) 1985 (Robert F. Curl. Jr.), (Harold W. Kroto),
(Richard E. Smalley) 1 ' (buckyball)'
(buckminsterfulle rene) .
(9) 1986 (K. Eric Drexier)
, ' (Enginess of Creation)' .
(10) 1989 IBM (Donald M. Eigler) (xenon
atoms) .
(11) 1991 (Tsukuba) NEC (Sumio lijima)
.
(12) 1993 (Warren Robineet) UCL A
(R. Stanley Williams) STM
.
(13) 1998 (Delft University of Technology)
(Cees Dekker) .
- 14 -
(14) 1999 (Rice University) (James M. Tour)
(Mark A. Ree) , .
(15) 2000
.
(16) 2000 ,
.
(1)
Neal Lane 1998 4
" 21
." .
(President
Clinton's Cabinet-level National Science and Technology) , ,
' ,
(Interagency Working Group on Nanoscience, Engineering &
Technology, IWGN
)' 1999
(Nanotechnology Research Directions, http.//www.nanao.gov )
21
.
IWGN 2000 ' (National
Nanotechnology Initiative)' 270
2001 495 .
5,940 2001 41,000
(4 1000 ) 14.5% .
,
2002
3 - .
" "
(www.most.go.kr ) .
( ) 10 1,180 , 1,850 , 3,030
. 4
100 , 10 20 , 20
10 .
- 15 -
,
.
IWGN 20 ,
, ,
.
3 , ,
,
,
.
(2)
" ( )
, " .
Roald Hoffmann
. "
."
- 16 -
.
(valence band) (conduction
band) .
. 400 800 nm
100 nm
.
.
.
.
,
, Horst Stromer
.
IWGN 10
8
-
.
.
.
- 17 -
.
, " " 100%
.
(self-assembly)
.
.
, , ,
.
. IBM J. Armstrong
1991 .
(atom) (molecule)
.
, ,
.
.
- 18 -
. 15
. ,
.
( )
.
.
top-down
100 nm .
bottom-up
.
1 2 nm
.
bottom-up .
.
.
.
- 19 -
2.
.
' ' '
' .
,
.
.
, , , ( ) , , , ,
, . , ,
.
. IT( )
BT( ) .
.
- 20 -
,
.
.
,
.
.
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.
DNA .
.
,
.
, , ,
.
50
.
- 21 -
.
( )
.
.
.
,
.
.
.
.
( )
.
.
10 20 .
- 22 -
(2) ( )
2015
.
.
, ,
,
.
(RAND) "
, 2015 "
.
.
(3)
.
2015 .
DNA
.
.
- 23 -
, .
, 2015
.
,
.
.
( ) .
.
(4)
.
, .
15
, .
.
- 24 -
.
.
(5) MEMS
MEMS(microelectromechanical system)
.
.
< 1-1>
(nano-processing)
, , , , , , , , , , , , , ,
, ,
(nano-structuring)
0, 1, 2, 3 , , , , , , ,
, , , , ,
(nana-functions)
, , , , , , , , , , , ,
, , , , , , , , , , , , ,
(nano-components& systems)
, , , NEMS, , CMOS, , , ,
, , , , , , , , , ,supercapacitor
- 25 -
< 1-2>
, 5
, ,
,
, ,
, , 3
/ /
100 3
, ( )
, , , ,
,
- 26 -
2
1.
.
, , (EU) 3 .
(IT) (BT) (NT)
.
,
.
, , (EU) . ,
,
. , ,
1990 21 .
,
, ,
- -
.
- 27 -
11% , ,
, .
2000 1 Clinton NNI(National Nanotechnology Initiative)
, , ,
,
.
3 , Nano materials,
Nanoelectronics, Bionanotechnology . Nano-materials
, , , ,
.
Nanoelectronics ,
. Bionanotechnology , , ,
,
.
,
.
(1)
, 21 3
. . 1998 12
' (NNI)'
. (NSF)
, , (NASA), ,
.
- 28 -
12 (NNI : National Nanotech
nology Initiative) 21
2001 56% 4 2,300
2000
BT, IT .
(2)
IT NT .
. ,
.
. 2003 50
.
.
NNI 2001 6
2001 3 9600 ( 23.8% ) 2003 NT
BT . , ,
.
- 29 -
(3)
EU ,
. EU 2003 4 ' 6 '
.
EU 2003 2005 3
, .
( )
(BMBF) , , , ,
, .
( )
(National Initiative On Nanotechnology)
, .
- 30 -
( )
French Club Nanotechnologie CNRS
.
( )
TOP NANO 21 .
( )
ARC(Australia Research Council) 2000 9
.
(4)
( )
2001 5 NNI
. S863
5 ,
, , , , ,
.
( )
ITRI(Industrial Technology Research Institutes), NSC(National
Science Council),
MOE(Ministry of Education) .
- 31 -
.
1995 NRL, SRC, RRC, ERC,
, 21
(KIST : Korea Institute of Science and Technology)
.
, , ,
, SK , LG , ,
,
.
.
.
21
3 10 1 4000
2010 10
.
- 32 -
10 (BT)
,
(NT)
.
1999 2008
69
2 3 .
93 5000
. , , / ,
, 5
/
.
( , , ,
KAIST) ( , , , KAIST, ,
, , , , ) RRC/SRC( ,
, , )
.
- 33 -
10 20 ' 2
' , ,
.
10 20
. 10
.
.
.
2.
(NanoBio technology) ,
21
.
- 34 -
, ,
, ,
.
.
.
.
.
.
.
, ,
,
. DNA
' ' .
- 35 -
.
(multi-infarct dementia) (advenced
Alzheimers disease) (chronic degenerative brain diseases)
. ' ' ,
.
.
, ' (bio-electronics)'
. ' ' '
' . .
(biochip) 1980 .
1961 30
.
10-20 .
2 3
. .
100,000,000 .
- 36 -
' '
' ' . ,
, , .
' (biocomputer)'
.
.
' ' ' (nanocomputer)'
. ' ', '
' . .
, .
, ( ) ( )
.
.
.
.
. .
- 37 -
(biosensor) .
,
.
.
, (MEMS) . 1988
(Richard Muller) 3 2
500 ,
(Jeff Sniegowski)
.
6 ( 1 )
2 .
,
.
(Paul Mcwhorter)
100
.
.
.
. .
.
- 38 -
. (Bill Degrado) . "
.
.
."
, ,
.
. 21
30
.
. . "
.
,
,
."
SPM(scanning probe microscope)
.
- 39 -
Paul Scherrer Institute Ros AFM
( ( 50pN)
. IBM Zurich Basel MEMS
1/50 ' ' DNA
Science(Fritz et al., 2000)
-
.
1998 Noji Hiroyuki "
(molecular moter)" Amerisham Pharmacia Biotech and
Science Prize . ATP
F1-ATPase (actin filament)
,
.
(drug delivery system)
, MEMS
.
Cormell Nanobiotechnology Center nano-micro fabrication
(nano-fluidics) DNA (biofluid)
.
.
. / , receptor/effector, /
.
- 40 -
,
(nanobiotechnology)
.
?
,
. 1
column detector
HPLC
.
neuro neuro-computer ,
.
, , interdisciplinary program
.
, ,
.
, , , (nano-biosystem)
, .
- 41 -
- ,
, ,
.
(dendrimer) .
3 440
(dendrimer)
5 .
4 5
, , , ,
(smart bomb) .
NIH
DARPA(Defence Advanced Research Project Agency)
Dr. James R. Baker Jr Center for Biologic Nanotechnology
.
- 42 -
, , , ,
.
(dendrimer)
.
(micellar nanoparticle)
,
.
(nanoemulsion) 400 800 nm
.
' (Se) ' (
) ,
.
12 ' 5 7 '
20 ( 3,200 ) ( )
' ' '
.
.
.
.
- 43 -
10
[ ( )] .
.
, , .
( ) ( ) .
.
.
.
KAIST ,
.
(GMR)
(TMR), , 10
.
- 44 -
.
10 200 nm
.
.
,
, .
,
.
,
.
.
(NASA) MIT,
.
.
- 45 -
< 2-1>
( : )
( )
/
(7 )
, (1) 1(5) /
, , , , (5) 3(30) /
, , , (10) 2(10) /
, , , , (5) 5(50) /
, , (3) 3(30) /
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( ) (MEMS), , , (0.5) 5(30) /
(2 )
(0.1) 1(0) /
, , , , (5) 4(10) /
/
(23 )
,
,(0.5) 1(10) /
,
,(0.5) 1(20) /
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, (0.1) 1(0) /
, , (0.01) 1(20) /
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( ) , (1) 5(10) /
( ) , (1) 1(0) /
, (0.1) 2(5) /
(0.1) 2(10) /
(3) 1(0) /
Biomineralization , , , (1) 1(5) /
(1) 3(4) /
(1) 1(5) /
- 46 -
< 2-1> ( )
( : )
( )
/
/
(23 )
, , , (1) 3(10) /
/
(0.1) 1(10) /
1(0) /
(1) 5(10) /
Phantom
-(5) 1(3) /
, (1) 1(0) /
(1) 2(5) /
, (1) 1(10) /
(7 )
(1) 1(20) /
, , (1) 3(20) /
(1) 1(10) /
( ) , (0.5) 3(30) /
,
(1) 1(20) /
, (0.5) 3(20) /
, (1) 4(30) /
,
,
,
(11 )
100nm
(0.5) 2(5) /
, , , , (1) 4(40) /
4(20) /
5(10) /
1(0) /
3(3) /
1,2 5(10) /
(1) 1(0) /
(1) 1(3) /
5(20) /
/ / (1) 5(30) /
- 47 -
3.
(WTEC)
5 42 (164 ), (151 ), (149 )
. 5
.
, , 10 ,
6 3 1 4 1
.
. .
.
.
100 25 .
( ) ' '
.
5
49 (275 ) 5 1 . 185 ,
125 .
"
." .
- 48 -
< 2-1>
< 2-2>
(1976 1999 ) 13
(15 ), (14 ) 18 .
4298 , 714 , 273 .
- 49 -
(1988 1996 ) 30 2062 ,
649 , 547 . 505 , 345 , 249 ,
219 , 162 .
< 2-3>
< 2-4>
- 50 -
2001 7 10 1 3725
5 .
3 , , 34
13,000 ,
Fab .
25%
10
.
- 51 -
3
1.
.
.
,
.
.
.
.
. , ,
.
- 52 -
, ,
,
, , ,
, , , ,
.
, .
.
, .
, , ,
.
, ,
.
- 53 -
.
, ( ) , , , ,
.
,
.
" (nanotechnology) (IT,
information technology) (BT, biotechnology)
" .
,
. , ,
, , .
. ,
(interdisciplinary) .
.
. , ,
, , ,
. , ,
.
- 54 -
2.
.
,
, ATP
.
, Nano-copter + + DNA
+ Fe+2 ( ) complex
.
, Lab-on-a-chip , chip
,
. .
, + +
.
- 55 -
3.
' ' .
,
.
.
DNA
(Oligonucleotide) cDNA , ,
.
100 1,000 DNA DNA DNA
DNA
, DNA DNA
. "
" .
< > , "
"
" ' ', "
. "
, 2010
" .
.
. ,
, , 5 1
10
.
- 56 -
" '
' 21 ' ' " .
< > "
,
" "
" .
"
' '
" .
.
, .
.
. .
.
.
.
.
- 57 -
,
.
.
,
.
21 .
.
.
- 58 -
1. , , , , 13, 38, 2000
2. 31 , 21 , , 1994
3. , , , 1994
4. , , , 1995
5. 3 , , , 1995
6. "Atom by Atom, Scientists build Invisible Machines of the
Future". Andrew
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53. , (2000)
- 62 -
. (Nano Fluidics)
/
/
- 63 -
1
1.
21 , , ,
.
10 1(10-9 ) , 1
100 .
,
.
, ,
.
.
(Information Technology : IT), (Bio Technology : BT),
(Environment Technology : ET) 21
.
- 64 -
,
(Bio Technology)
. (Genome-project)
,
.
.
.
.
21
. ,
,
, .
,
3 .(< 1-1> )
,
.
- 65 -
< 1-1>
2.
.
. ,
.
. ,
, (DNA chip),
(protein chip), (cell chip) .
- 66 -
(1) DNA (DNA Chip)
DNA ( ) DNA ,
DNA (capture
probe) ( ) .
(Oligonucleotide chip) cDNA (cDNA chip)
, . DNA
(DNA chip) DNA DNA
(hybridization) , (staining) (laser
induced fluorescence),
.
(2) (Protein chip)
DNA .
(protein) (ligand)
.
, (ligand),
(ligand)
,
.
- 67 -
(3) (Cell chip)
,
.
,
.
.
.
(glass) (polymer)
.
(hard-ware)
(wet-ware :
nanofluidics) .
- 68 -
(1) (Nano-hardware)
(bulk micromachining)
(surface micromachining) . ,
, ,
.
.
.
. , ,
.
(polydimethylsiloxane : PDMS)
(polymer) .
(polymer) (chamber)
(polymer) (polymer)
. PDMS
.
- 69 -
(polycarbonate : PC),
(polydimethylmatha- crylate : PMMA), (polystyrene : PS)
.
(hot emblossing) .
. kN .
, ,
, .
(polydimethylmatha-crylate : PMMA)
. , ( ),
.
5 10 .
,
.
,
.
- 70 -
. (Nano-wetware)
(nanofluidics) .
100
,
.
(MEMS) 100nm
100nm
.
.
.
.
.
, .
- 71 -
2
,
, .
, .
1.
.
1999 " 21
, , , , ,
"
, ,
.
.
- 72 -
.
, .
, , 1990 21
.
,
(Genomics),
(Bioinformatics), - -
(Proteomics)
. 11%
, , , .
(1)
2000 1 "
2001 5
. ,
.
- 73 -
, 2000 1 NNI(National
Nanotechnology Initiative) , 2001
56% 4 2
, 1Tb , ,
.
,
, NSTC(National Science & Technology Council)
NSET(Nanoscale Science, Engineering, and Technology) .
NNUN(National Nanofabrication User Network) Stanford
5 < 2-1> .
< 2-1> NNUN
- 74 -
< 2-1> NNUN
Cornell University micro & nanofabrication, e-beam
lithography
Stanford University micro & nanofabrication, Si
UC Santa Barbara ( )
Penn StateUniversity
micro & nanofabrication,nanofabrication
Howard University Wide band gap (SiC , )
3 5
.
(2)
(BMBF) 1998
, 1998
5 , . ,
, , , .
- 75 -
(3)
1988
(LINK) , 200 . 1994 1997
700 .
.
(4)
CNRS(CENTRE NATIONAL DE LA RECHERCHE SCIENT-FIQUE)
2%( 4,000
) , , , ,
, , , ,
.
(5)
TOP NANO 21 , ,
.
- 76 -
(6)
,
2001 50
.
, 5
,
.
, .
2000 12
, 2001 3 .
2001 25% 4 .
90
.
, .
NNI(National Nanotechnology Initiative)
.
- 77 -
(7)
2000 1,300 ,
2000 ' ' 1,300
.
2000 1,200 ,
, , , .
.
(1) (Protein Patterning)
( )
(silane) . Kleinfeld
(silane) .
(Alkyltrichloro silane)
, (amino-trihydroxy silane)
. 50
.
EDS(N-(2-aminoethyl)-3-amino-propyltrimethoxysilame)
DMS(dimethyl
dichlorosilane) .
(silane) DMS(dimethyl dichlorosilane) (methyl)
(amine)
.
- 78 -
DMS(dimethyl
dichlorosilane)/EDS(N-(2-aminoethyl)-3-amino-pro-
pyltrimethoxysilame)
.
.
(silane)
.
. (silane)
.
.
( )
(photochemical method)
. (thiol) .
(arylazide), (nitrobenzyl),
(diazirine) .
, ,
.
- 79 -
. (UV light)
.
, BSA
.
.
.
< 2-2> (Light-directed parallel chemical synthesis)
- 80 -
,
Schena
.
( ) (SAMs)
(Alkyl sliane) (alkane thiol)
.
.
(monolayer) (monolayer)
(< 2-3> ).
< 2-3> (Au 111) (Self assembled monolayer on
Au(111))
- 81 -
(monolayer)
.
.
.
Williams .
(coupling agent)
. N-succinimidyl 3-(2-pyridyldithio)
propionate(SPDP) (SAM) ,
2,2,2,-tri-fluoroethanol(TFE) .
STM(scanning tunneling microscope) (hydrogen
peroxide) .
. TFE
.
.
(SAMs) (amphiphilic) (highly
ordered monolayer film) . , ,
. (SAMs) ,
, QCM(quartz crystal microbalance) .
(absorption site)
Langmuir adsorption kinetic . Pylant (Au 111)
(alkanethiol) (self-assembly)
. STM(scanning tunneling microscope)
(Au 111) (alkanethiol) .
- 82 -
Biebuyck microcontact printing
. (stamp, PDMS )
, 1 99%
.
.
microcontact printing (softlithography)
Whitesides . Whitesides microcontact
printing( CP) 25 m 1
(SAMs) . (photography), (e-beam
lithography) , microcontact printing (
CP) ( ).
< 2-4> CP A) B)
C)
- 83 -
( PDMS) (hexadecanethiol, HDT,
CH3(CH2)I5SH)
(SAMs) .
(NSB, Non-specific binding)
(non-specific binding)
. (Non-specific binding)
(assay)
.
(silane) (alkane monolayer)
(SAM)
. BSA (casein)
. (PEG)
PEG
.
- 84 -
.
(fluorescently tagged protein) (fluuorescence microscopy)
.
. SEM(Scanning Electron Microscopy)
.
(protein coverage) .
AFM(atomic force microscopy)
.
( ) (Surface modification and protein immobolization)
.
.
.
Huang avidine-biotin link . BSA
(biomolecule) MeNPOC-biotin
MeNPOC-blotin-BSA
(protecting group) biotinylated antibody, avidin
streptavidine .
- 85 -
Cathignol 3-cyanopropyl dimethyl chlorosilane
.
cyano group . Mouse anti-rat
CD45RC (ELISA) .
Bates Thiabendazole , ,
. APTS
.
. 0.1N
.
(solid-liquid) (affinity
interaction) .
.
RIFS(Reflectometric interference spectroscopy)
, (nonspecific adsorption)
.
Immunophore
, , ,
.
(ligand) (active site) .
- 86 -
. , (affinity interaction)
.
< 2-5>
- 87 -
Pihler , , PEG, poly(ethyleneimine), poly(acrylamide)
(ligand) RIFS
(nonspecific protein adsorption), (specific antibody
binding),
. RIFS (oligomer)
(monoalkoxy silane)
(amine group) succinic anhydride (carboxyl group)
. (heptan)
(specific binding) .(< 2-5> )
(2) (Nanoscale flow control)
( )
,
.
/
-
(surface-to-volume ratio) DNA RNA
(macromolecule) (surface potential)
(Wan effect) .
(viscosity)
.
- 88 -
( )
,
(hydrodynamic force) (electrokinetic force)
.(< 2-2>,< 2-6> )
< 2-2>
- /
- (Re ( ) ( )
- 89 -
( )
Harvard University(George Whitesides Group)
G. Whitesides
(7 layer flow)
.
(microfabrication)
.
< 2-7>
( ) ( )
- 90 -
Oak Ridge National Laboratory(Ramsey Group)
Ramsey
,
. .
< 2-8>
Technical Univ of Denmark(Larsen Group)
Larsen
,
.
< 2-9>
- 91 -
Tokyo University(Kiamori Group)
Kiamori
.
< 2-10>
- 92 -
(3) (Single Molecule Detection)
( ) (Optical tweezer) (single molecule detection)
, ,
.
/ . ,
, , ,
/ .
/
.
(Nano-hydrodynamics)
. (molecular effect)
.
, ,
.
- 93 -
(Optical tweezer) (magnetic tweezer),
DNA (single
molecule detection) (control)
.
(manipulation)
(optical tweezers) (optical traps)
.
(refractive index) (
polystyrene sphere )
(momentum) (optical path)
.
(radiation pressure)
. (optical tweezer)
, .
(sphere) (intensity
gradient) (gradient force)
(scattering force) ,
(gradient force) .
- 94 -
,
,
.
(scattering force) (gradient force) ,
(numerical aperture : NA) (
submicron 100 ) (gradient force)
.
1986 AT&T Bell A. Ashkin CW laser
, Ar+ laser Nd : YAG laser
. < 2-11>
(optical tweezer) .
< 2-11> (Optical tweezer) (particle
)
- 95 -
( ) (Single Molecule Detection )
(biological macromolecule)
. (micro flow) ,
(microdevice) (surface to volume ratio)
(viscous force) (surface force)
.
DNA (biological macro-molecule)
(non-Newtonian effect)
. (polymer relaxation time)
Deborah number . (nondimensional parameter)
Deborah number (shear rate) (polymer relaxation time)
(polymer stretching) .
Single-Polymer Dynamics in a specific How : Steven Chu group
(polymer molecule)
1934 W.Kuhn 60 .
(non-Newtonian How)
(elongational flow) (birefringence),
.
- 96 -
.
(elongational flow)
.
Steven Chu group
Steven Chu 1977 'Method of cooling and trapping
atoms by using laser light' .
(elongational flow), (sudden elongational flow),
(steady shear How) DNA
.
(Elongational flow)
(entropic elasticity)
.
. (Brownian motion)
.
(nondimensional parameter)
Deborah number (polymer stretching)
.
- 97 -
< 2-12> Chu (optical tweezer)
< 2-12> (bead) DNA
(optical tweezer) . DNA
(stretching) . Chu
DNA
< 2-13> .
< 2-13> DNA (relaxation)
- 98 -
Chu 'Response of Flexible Polymers to a sudden Elongational
Flow'
, (elongational flow)
< 2-14> A) ,
< 2-14> B) (stretching)
5 .
(Elongational flow) DNA
hear flow) .
video fluorescence microscopy
Chu C) .
< 2-14> A) (sudden elongational flow) T
B)
- 99 -
< 2-15> A) (Shear flow) , B)
(stretching) , C)
< 2-15> A)
.
(drag force) DNA
(stretching)
.
< 2-15> B) (Brownian motion)
(stretching) (tumble)
.
(biomolecule)
.
- 100 -
< 2-16> (Steady shear flow)
Single-Polymer Dynamics in a specific now : Liepmann group
UC Berkeley Dorian Liepmann
.
< 2-17> Liepmann
reservoir .
(photolithography) (Deep RIE) (channel)
(reservoir) , (epoxy) (upper layer)
(bonding) .
- 101 -
< 2-17> Liepmann
Liepmann
(reservoir)
(elongational flow) (shearing flow)
< 2-18> < 2-19>
.
< 2-18> DNA
- 102 -
< 2-19>
< 2-18> A, B, C, D, E, F DNA
(elongational flow) DNA (stretching)
.
DNA , ,
. Liepmann
Deborah number
. Deborah number ,
.
Liepmann DNA
.
.
- 103 -
DNA molecule assembly under uniform shear flow : Denis Wirtz
group
(Johns Hopkins University) Denis Wirtz
(magnetic bead) DNA (magnetic force)
DNA
. DNA
, DNA .
Ajdari et al 1994 .
Wirtz 'Shear-Induced Assembly of -Phage DNA'
(uniform shear flow) DNA
.
< 2-20>
- 104 -
< 2-20> (Rheometer)
(shear flow field) .
DNA (multimer) .
DNA (shear induced DNA assembly)
.
(Gel electrophoresis) DNA
Wirtz (chromosom mapping)
(gene chip)
DNA .
.
2.
.
2002 5 . 2001
12 , 2002 2 "
" , 5 " " 1
.
- 105 -
2001 7 10 1
3,725 5 . 3
, , 34
13,000 ,
Fab .
/ 25% 10
.
2002 " - " 2010 (NT) 5
, (BT) 7
(NT 14 , BT 17 ) . NT
BT 10 1 5 10
, , ,
500
.
- 106 -
.
,
( )
,
.
(1) (flow cytometry)
( ) (flow cytometry)
. Agilent ,
, (flow cytometry)
. , ,
.
,
.
(2) (lab-on-a-chip)
( ) ,
,
(Electrochemical detection),
(Electrochemical detection) .
- 107 -
,
(Lab-on-a chip) .
, (hemocytometer)
ABO ,
,
.
(3)
10
.
,
, .
, ,
nm
(Micro-PIV)
,
.
- 108 -
(Micro-PIV)
.
,
, , ,
.
.
3.
, ,
, (now cytometry) (macro)
, , ,
, , ,
.
, (flow cytometer)
,
.
- 109 -
,
, .
< 2-21>
.
< 2-21>
- 110 -
< 2-3> .
< 2-3>
,
,
MEMCAD, CFDACE CFDACE+
Cr , X-ray
Cr
SU-8, ,
, ,
, ,
, ,
,
< 2-4> (flow cytometry)
3 ,
3
LIF, scattering LIF, scattering
,
, ,
,
- 111 -
3
1.
.
.
1990
. 1996
, 21
.
,
, MEMS
.
- 112 -
.
,
.
2002 " - " 2010 (NT) 5
, (BT) 7
(NT 14 , BT 17 ) .
,
, ,
. .
(1)
(2) DNA
(3) DNA
(4) (microbead) (optical tweezer) DNA
(5) DNA ,
(6) DNA (RNA , DNA )
(RNA DNA )
(7) DNA
(8) DNA
(9) , (ligand) DNA
(10) (nanopore) DNA
- 113 -
2.
.
21 . ,
, , 21
.
IT(information technology)
,
. , , ,
.
- 114 -
.
/ , 21
.
, .
2000
. 1990 < 1-2>
,
2000 21
.
< 3-1> (1995 2005 )
, , (concept)
.
,
.
- 115 -
.
. , IT
. ,
,
.
3.
10
20 . 20
500 2,000 .
2001 'Nano Business Alliance
30% . ,
. NSF
2010 1 .
Ernst & Young 2008
.
- 116 -
< 3-2> ( )
< 3-3> ( )
< 3-1>
,
.
< 3-1>
- 117 -
< 3-4> DNA chip Protein
chip / chip Lab chip
/
.
< 3-4> (Bio Chip) ( )
4.
, ,
, ,
. ,
,
.
,
.
- 118 -
5.
.
. ,
.
,
, . ,
.
- 119 -
, ,
, ,
, .
, .
, ,
, .
,
.
,
, ,
.
- 120 -
1. Bechman Institute for advanced science and technology. Annual
report 2001
2. David Rotman, Nanotech goes to work, An MIT enterprise
Technology review,
Jan./Feb.2001 (http://www.technologyreview.com/)
3. (http://www.most.go.kr/)
4. Philip S. anton. Richard Silberglitt. Jamse Schneider, The
glabal technology
revolution, National Defense Research Institute
5. , , . 2001
6. Jonathan Freund, The nanofluidics and biology group,
proceedings of the summer
program 2000
7. Andrew F. Diad et al, An electrochemical detector array to
study cell biology on
the nanoscale, Nanotechnology 13 (June 2002) 285-289
8. H. G. Craigheadl. Nanofluidic systems for biomolecular
analysis Frank J.
Steemers, Jane A. Ferguson. and David R. Walt, Screening
unlabeled DNA targets
with randomly ordered fiber-optic gene arrays. volume 18, 91-94,
January 2000
9. Minyoung Han. Xiaohu Gao, Jack Z. Su. and Shuming Nie,
Quantum-dot-tagged
microbeads for multiplexed optical coding of biomolecules,
volume 19. 631-635, July
2001
- 121 -
.
/
/
/
- 122 -
1
1.
21
(NT), (BT), (IT) .
. ,
.
20 , , , , , ,
,
. 21 IT
BT ET , , , , , ,
, .
21
- 123 -
. IT ,
BT .
/ , , , , , , , ,
, , , ,
, , ,
.
,
. 1
(column) (detector)
HPLC
. (neuro-computer)
, .
, ,
.
DNA .
.
,
, ,
.
- 124 -
50 nm
.
. (
)
.
2.
(superparamagnetic)
. (coercivity)
. -
< 1-1> [1,2].
(single domain) (multi domain)
.
domain wan motion ,
domain wall
spin rotation(domain rotation) .
- 125 -
< 1-1>
zero .
(spin) (thermal effect)
.
.
- 126 -
( )
.
.
(modification) .
(cell separation)[3,4] (cancer hyperthermia)[5,6]. MRI
(contrast agent)[7,8,9] (localized drug
carrier)[10,11,12] .
(biomedical applications)
.
- 127 -
2
1.
.
1970 (Magnetic Resonance Image, MRI)
. ,
, . , ,
MRI .
.
MRI , ( )
, .
, (voxel) , ,
. MRI
.
.
- 128 -
< 2-1> MRI
/ . MRI
, ( )
. MR ,
.
Fe, Mg, Gd, Dy ,
Fe3+, Mg2+, Gd3+ . Dy3+ .
.
.
. ,
.
- 129 -
-DTPA FDA MRI ,
Gd3+ ,
. Gd-DTPA-BMA,
Gd-DOTA Gd-DO3A .
,
.
, .
Gd-DTPA . Gd-DTPA
.
Gd-DTPA , , MRI
l . ,
Gd-DTPA ,
.
(superpara-magnetic iron oxide,
SPIO) .
.
SPIO , MRI . SPIO
,
. MRI
.
- 130 -
5 nm (super-para-magnetic iron oxide,
SPIO : < 2-1>) . 10-20
nm , (surface modification)
. SPIO 20 nm , 720 kDa
.
SPIO T2 label ,
. Trasferrin, ferritin, hemosiderin, hemoglobin
, SPIO
. (50-100 mg, 0.01-0.02mM Fe/Kg)
( 3500 mg) .
(X-ray computed tomography, CT) MR
, Gd-DTPA
CT 1/100 .
< 2-1>
- 131 -
.
. (intravenous, IV)
.
.
, (permeability) IV .
,
(capillary endotheliallining cell) .
(blood-brain
barrier, BBB), GD-DTPA
. BBB
, (specific
targeting agent) .
, , , .
6-50 nm , (fenestrated
capillary) .
, .
,
, . 6 nm
(macromolecular)
20 kDa , 50 kDa .
- 132 -
Gd-DTPA(n=15-35)
(backbone) . MR
, ,
.
, .
.
Albumin-(Gd-DTPA)n
(synthetic backbone) . Dextran-(Gd-DTPA)15
polylysine-(Gd-DTPA)40-60 ,
, .
, ,
Kupffer RES blood pool agent
. 110 Gd-DTPA .
nm Kupffer , ,
(macrophage) RES .
(sinusoid) 100nm . , RES
. (AMI-25, SPIO)
80 nm , .
. ,
RES .
.
- 133 -
AMI-25(80 nm) SHU-555A(60 nm) SPIO 8 10
.
. RES threshold
20 nm . AM-227 20 nm, 200 ), MION-46(18-24
nm 180 ), Gd-DTPA-PGM(18 nm 120 )
SPIO ,
(interstitium) , (capillary endothelium)
.
(mononuclear phagocytic system) ,
, . 20 nm
IV ,
.
(antibody)
. (monoclonal antibody)
SPIO .
, , RES
. 20 nm RES
, 20 nm
.
- 134 -
2. (Magnetic Drug Targeting)
.
.
. .
. , .
.
, , .
, , , ,
.
,
. ,
.
. , .
, ,
.
.
(1)
:
(2) .
- 135 -
.
,
(reticuloen-dothelial system, RES)
. < 2-2>
[13].
,
.
.
.
, , ,
. ,
immunomagnetic bead
.
- 136 -
< 2-2>
,
( : >10 cm/s, : >0.05 cm/s)
.
, .
,
. ,
. , RES
, ,
.
.
- 137 -
( )
, MRI
.
Au-Magnetite -
[14].
< 2-3> .
.
,
. ,
.
< 2-3> TEM
- 138 -
.
Epirubicin (solid tumor)
. L u ubbe .
epirubicin ( 100 nm)
.
epirucixin .
LD50 ,
.
Phase I/II
. 9
.
, .
.
, , .
.
(1) ( , , , ,
, )
(2) ( , , , )
(3)
(4)
(5) ( , , , , ,
, , )
- 139 -
3.
Bioseparation downstream processing BT
. BT ,
, .
.
.
(magnetic separation)
. , , (tissue homogenate),
, , .
,
electromigratory
. .
, ,
.
- 140 -
,
. ,
.
.
, .
,
(erythrocyte)
magnetotactic bacteria .
.
, .
, (epitope) (antibody)
. , .
, .
- 141 -
3 .
(1) .
( 30-60 ) . ,
, .
(2) .
.
, (chromatography, electrophoresis, PCR )
.
(3)
. ,
.
.
magnetotactic bacteria
. magnetic labelling ,
, magnetoliposom . Fe3O4
-Fe3O4 , .
1 50-200 nm
.
. ,
.
.
.
- 142 -
.
(1) .
(2) .
(3) .
(4) .
(5) labelling labelling
.
(6) .
< 2-2> .
labelling .
[15]
[16,17].
- 143 -
< 2-2>
Name Diameter( ) Manufacture/supplier
BioMag ~1 PerSeptive Biosystems, USA
Dynabeads 2.8 - 5 Dynal, Norway
Estapor ~1 Prolabo, France
Iobeads ~1 Immunotech, France
MagaBeads 3.2 Cortex Biochem, USA
Magne-Sphere < 1 Promega, USA
Magnetic beads 0.8 Prozyme, USA
Magnetic microparticles 1 - 2 Polysciences, USA
Magnetic particles 1 Boehringer, Germany
MPG 5 CPG, USA
Sera-Mag 1 Seradyn, USA
SPHERO 1 - 4.5 Spherotech, USA
XM200 3.5 Advanced Biotechnologies, UK
Ferrofluids 0.135, 0.175 Immunion, USA
MACS microbeads 0.05 Miltenyi Biotec, Germany
Magnetic nanoparticles 0.1 - 0.6 Micro-caps, Germany
MagNIM 0.05, 0.25, 0.5 Cardinal, USA
.
, . Immunomagnetic separation(IMS)
. IMS 1979
Kemshead .
neuroblast , .
- 144 -
< 2-3> immunomagnetic separation
Microorganism Magnetic particles Analysed sample
Actinobacilluspleuropneumoniae
Dynabeads M-280,sheep anti-rabbit IgG
Tonsils
Aeromonassalmonicida
Dynabeads M-280,sheep anti-mouse IgG
Salmon lice
Clostridium difficileMagnisort coated with goatIgs specific for
murine IgGand IgM
Stool samples
Ehrlichia risticiiDynabeads M-280, sheepanti-rabbit IgG
Horse faeces
Escherichia coli O157Commercially availableDynabeads anti-E.
coli O157
Stool samples
Mycobacteriumtuberculosis
Amine-terminated BioMagCerebrospinalfluid
Thermodesulfobacteriummobile
Dynabeads M-280,sheep anti-rabbit IgG
Water samples
Vibrioparahaemolyticus
Dynabeads M-280,sheep anti-rabbit IgG
Food samples
Yersiniaenterocolitica O:3
BioMag Faecal samples
.
. ,
, IMS
. ,
.
gradient centrifugation . 75%
, 95% [18].
- 145 -
< 2-4> (Dynabeads)
. .
< 2-4> T-lymphocyte Dynabeads M-450
.
. Dynal 99%
Dynabeads M-500 Subcellular .
IMS [19] < 2-5> .
, .
,
. ,
.
.
[20].
- 146 -
< 2-5> IMS
4. (hyperthermia)
.
41 46
(hyperthermia) . ,
.
(42 43 )
. , ,
.
, , .
. pH 7.2 7.4
pH .
- 147 -
Amino acid
thymidine , , insuline
. polyamine , DNA
, cellular polymerase
.
. cytoplasmic protein
nuclear protein DNA
[21].
, ,
.
45
.
Hyperthermia
minimally invasive, toxic
.
.
< 2-6> [22].
- 148 -
< 2-6>
.
1960 AC
. , 90
, .
1993 Jordan
[23].
- 149 -
(single domain) (multi domain)
1000
. Brownian relaxation(
) Neel effect( )
,
[24].
.
,
.
glioblastoma prostate
carcinoma cell ,
.
,
, .
,
. ,
.
,
. , , ,
, , , ,
.
- 150 -
2000 Clinic of Radiation
Oncology Charite Medical School . MFH
Hyperthermiesysteme GmbH(Berlin, Germany) 100kHz
. 30 45cm ,
0 15kA/m .
5.
. Co, Fe, Ni
(Magnetite, Maghemite) . ,
.
, ( )
.
. , ,
.
- 151 -
. ,
. ,
,
, , ,
.
,
.
.
87 15
2 DDS
1/3
.
, 90 ,
92
.
- 152 -
3
1.
.
< 3-1> 20%
2007 500 1200
.
10 Alza
Corp. 1999 , 2000
. Alza Corp. 3 2
.
. Alza
.
,
.
- 153 -
< 3-1>
68 (97 ) 500 (2007 )
895 (97 ) 1,200 (2005 )
* : . SCRIP,
,
,
. 90
, l999
FDA , , 77 11
2000 6 30
.
.
Frost & Sullivan < 3-2> 1999 34
, 2006 42 . 1999
X- /CT 86.4% , MRI 13.5%, 0.06%
. X- /CT
MRI .
- 154 -
< 3-2> (Frost & Sullivan)
Advanced Nanoparticles 2004 MRI 11
.
.
,
.
,
.
- 155 -
2.
.
.
. ,
, .
.
.
10% (150 )
,
. ,
6,000 10,000 , 50,000 .
.
- 156 -
3.
,
. , MRI ,
.
,
.
. ,
, , , ,
.
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