nanoparticles for biomedical applications part i: preparation & stabilization jingwu zhang...
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Nanoparticles for Biomedical Applications
Part I: Preparation & Stabilization
Jingwu Zhang
5/3/06
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Nanoparticles for biomedical applications
Imaging agents Gold, Silver, Quantum
Dots, Magnetic Nanoparticles
Chemical sensors DNA Modified Au
particles Drug delivery devices
Nanocapsules Therapeutic agents (?)
Nano-sized delivery systems based on lipids and amphiphilic block copolymers
Conjugated Au particles stick to cancer cells
A cluster of gold nanoparticles 50 nanometers in diameter created a much larger crater in ice
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Outline
Preparation of monodisperse nanoparticles Gold nanoparticles Methods for achieving uniform particle size
Colloidal Stability in electrolyte solutions Surface charge DLVO theory Schulze-Hardy rule
Stabilization of Nanoparticles by polymers Polymer adsorption Stabilization mechanisms
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Preparation of Preparation of Monodisperse Monodisperse NanoparticlesNanoparticles
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Possible Applications of Colloidal Gold (C.W.Corti et al, Gold Bulletin 2002, 35/4 11-118)(B.Chaudhuri and S. Raychaudhuri, IVD Technology 2001 March)
Nanoswitch
Microwire
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Making Colloidal Gold: 1857 Faraday prepared gold colloids by reduction of gold chloride
with phosphorus. "Experimental relations of gold (and other metals) to light." In: Philosophical Transactions, 147, Part I, pp. 145-181, [1]. London Taylor & Francis 1857.
1861 Thomas Graham coined the word “colloid” to describe systems which exhibited slow rates of diffusion through a porous membrane.
Zsigmody (Nobel Prize, 1925) developed “seed” method to produce uniform and stable gold sols.
1908 Mie interpreted the vivid color of colloidal gold (Verification of Mie theory for light scattering).
1951 Turkevich, et. al. studied nucleation and growth of gold particles in sodium citrate (Discussions Faraday Soc. 1951, No. 11 55-75)
1973 Frens developed a simple sodium citrate reduction method to produce colloidal gold of uniform and controlled size.
Ref: M.A. Hayat “ Colloidal Gold” Vol 1, 1989
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Colloidal Gold Synthesis(Turkevich, et. al. Discussions Faraday Soc. 1951, No. 11 55-75)
Solution color varies extensively with particle size Usually a deep red, but also dark brown/purple
to light orange/yellow Colloid size can be controlled by Au:Citrate ratios
Anywhere between 1nm - 100nm Extremely stable
OH
HO
O
OH
O
O
HO
H2O, 100OCH2AuCl4
Cit-
Cit-
Cit-
Cit-
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Reduction by Citrate (Frens,1973)
Boil 50mL 0.01% HAuCl4 (0.29mM)
Add 1.75mL 1% Na3Citrate
Keep boiling for a few minutes
Mean particle size is 12nm (CV 20%)
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TEM images gold nanoparticles Produced by citrate reduction
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Homegeneous Nucleation
SgkTGV ln
Interface Energy r2
Volume Free Energy r3
r*
G
Gr
r
Gr*Free energy change for formation of bulk
Saturation Ratio:
S=C/Cs
C=concentration; Cs=solubility
Free energy change for generating the surface:
2
3
)ln(3
16
SkTGC
ΔGs=4πr2σ=4π(r/a)2γMaximum Gibbs free energy for nucleation
γ=surface energy per atomic site
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Homogeneous Nucleation Size Critical
Nucleus
Nucleation Rate
Activation Energy
SkT
arC ln
2 3
)/exp( kTGkJ Cnn
2
3
)ln(3
16
SkTGC
Sm
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Preparation of Uniform ParticlesStrategy 1: Control of nucleation
Monodisperse nanoparticles can be produced by confining the formation of nuclei to a very short period, so that the particle number remains constant and all grow together to the same size.
This strategy was first used by La Mer to produce highly monodisperse sulfer sols.
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1: HAuCl4 + 3e- = Au
2: Supersaturation build-up
3: Homogeneous Nucleation4: Growth of Nuclei 5: Stabilization by Dispersants
Steps for making Au nanocrystals
SAu
AuS
][
][
LmolAu S /102Solubility][ -12
[Au]
Metastable Zone: S=1 to Sm
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Preparation of Uniform ParticlesStrategy 2: Seeded Growth
Preparation of seed crystals Growth on seeds in meta-stable
zoneGrowth
2:1
3:2Diameter ratio
growth
4:3
The particle size distribution becomes narrower with time.
This strategy was first used by Zsigmondy to produce monodisperse gold sols
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Preparation of Uniform ParticlesStrategy 3: Aggregation of Nanosized Precursors
This strategy has been employed by Matijevic and co-workers to make a variety oftransition metal oxide by controlled hydrolysis techniques
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Hematite (α-Fe2O3) Prepared by Forced Hydrolysis (Matijević and Schneider, 1978)
2 4 6 8 10 12
-40
-20
0
20
40
/mV
pH
J. Zhang & J. Buffle, J. Coll Int. Sci 174 (1995) 500-509
50nm
pHiep=9.2
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Preparation of silver particles
AgNO3 + NaBH4
Na3Citrate
NaOH
Ag
Reducing agent
Stabilizing agent
pH Control
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Colloidal Stability in Colloidal Stability in Electrolyte SolutionsElectrolyte Solutions
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Mechanism of surface Charge Generation
Ionization of functional groups at surface
Ion adsorption from solution
Crystal lattice defects (clay mineral system, due to isomorphous replacement of one ionic species by another of lower charge)
OH
O-
COO-
X-
X-
X-
Si(IV)
Si(IV)
Al(III) Al(III)-
Al(III)-
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Electrical double layer
Helmholtz Model
Guouy-Chapman Model
Stern Model
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Colloidal Stability: DLVO TheoryDerjaguin-Landau (1941) & Verwey-Overbeek(1948)
22
2
22
2
2
2
44
4ln
44
2
4
2
6 RRss
Rss
RRss
R
Rss
RAA
)exp(64
2
200 s
kTRCR
Van der Waals Attraction
Electrostatic Repulsion
1
1
12 mmm ss
AR
Energy Maximum
2/12000
I
kT
eN A
sR
Sm = 3 nm for hematite
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Total interaction free energy
VT=VA+VR+VS
VS = steric repulsion
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Influence of electrolyte concentration on particle-particle interaction energy
Debye Parameter
К ~ I1/2 ~ electrolyte concentration
Double layer thickness (unit: Å):
К-1 = 3.04/I1/2
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Size Evolution vs. Ionic StrengthFe2O3: 10mg/L (2.4x1013/L), pH=3.0, 25.0±0.3°C
Critical coagulation concentration (CCC): The concentration of an electrolyte about which aggregation occurs rapidly
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CCC for selected sols
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Schulze-Hardy rule (recognized at end of 19th century)
(a) The CCC for similar electrolyte solutions is similar but not identical.
(b) It is the valency of the counter ion that is of paramount importance in determining the coagulation concentration.
According to DLVO theory:
CCC~1/z6
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Stabilization of Nanoparticles Stabilization of Nanoparticles by Polymersby Polymers
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Colloidal stabilization by polymers
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Examples of polymersSynthetic polymers
Biopolymers: protein, DNA, Polysaccharide
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Isotherm of polymer adsorption
(a) A typical high-affinity polymer adsorption isotherm
(b) Langmuir adsorption isotherm, usually followed by small molecules
Configuration of polymer chain on surface
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Mechanisms of Colloid stabilization by polymers
Increase in electrostatic repulsion
Decrease in attraction energy
Decrease in Hamaker
Constant Steric repulsion
Volume restriction Osmotic effect
H2O
H2O
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Destabilization of Colloids by Polymers
Polymer bridging Charge Neutralization Electrostatic Patch Model
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Double roles of polymers Flocculation and Stabilization
Steric stabilization
Charge reversal
Electrostatic & steric
Increasing polymer concentration
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Aggregation of Hematite by PAA (Mw=1.36x106)
0.0 0.2 0.4 0.6 0.8 1.0
-20
-10
0
10
20
30
40
/mV
Cp /mg l-1
0.0 0.2 0.4 0.610-4
10-3
10-2
10-1
100
Cp /mg L-1
Polymer Concentration (ppm)
Collision efficiency factor Zeta-potential
DLAPre-DLA
Post-DLA
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Effect of Molecular Weight
0 .0 0 0 .0 2 0 .0 4 0 .0 61 0-4
1 0-3
1 0-2
1 0-1
1 00 a
PA A / H e m a tite0 .0 0 0 .0 2 0 .0 4 0 .0 6 0 .0 8
-1
0
1
2
3
b
PA A / H e m a tite
u /
m c
m V
sE
-1
-1
Collision efficiency factor Zeta-potential
60.1
1069.3 4
nw
w
MM
M
53.1
1036.1 6
nw
w
MM
M
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Q&AQ&A
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Methods for determining particle size
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Dynamic Light Scattering (PCS)
PM
0
0
Time
Sca
tter
ing
In
ten
sity
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Instructor: Dr. Zhen GuoMatE 297, Spring 2006
Bonding Type IV – Van De Walls Force Bonding Type IV – Van De Walls Force from permanent and induced Dipolefrom permanent and induced Dipole
A B
A B
From Principles of Electronic Materials and Devices, Second Edition, S.O. Kasap (© McGraw-Hill, 2002)http://Materials.Usask.Ca
HC l
(a)(b)
(c)
Fig. 1.11: (a) A permanently polarized molecule is called a anelectric dipole moment. (b) Dipoles can attract or repel eachother depending on their relative orientations. c Suitably orienteddipoles attract each other to form van der Waals bonds.
T im e a ve ra ge d e le c tro n (n e g a tive c h a rg e )d is tr ib u tio n
C lo se d L S h e ll
Io n ic c o re(N u c le u s + K -sh e ll)
N e
From Principles of Electronic Materials and Devices, Second Edition, S.O. Kasap (© McGraw-Hill, 2002)http://Materials.Usask.Ca
A B
S y n c h ro n iz e d f lu c tu a t io n so f th e e le c t ro n s
v a n d er W a a ls fo rce
Instantaneo u s e lec tro n (nega tive charge)d istrib u tio n flu c tu a tes ab o u t the nu cleu s.
Fig. 1.13: Induced dipole-induced dipole interaction and the resultingvan der Waals force.