Laser Assisted Growth of Biodegradable Thin Films
James M. Fitz-Gerald
University of Virginia
Materials Science and Engineering
Email: JMF8H@Virginia.edu
(434) 243-8830
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Acknowledgements
Students: J. Hoekstra, C. Allmond, A. Mercado, C. Nelson
C. Fraser (Chemistry, UVa), L. Zhigilei (MSE, UVa)
R. Haglund, (Physics, Vanderbilt)
University of Virginia and the AFOSR for funding
Nanotherapeutics: J. Talton
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Outline
Applications for polymer thin films
Laser assisted techniques
Characterization and analysis
Conclusions
Future work
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Applications for Polymer Thin Films
Batteries
Data
Storage
Organic
Thin Film
Applications
Displays
Chem/Bio
Dielectrics
Sensors
Physical
Optical
Processing
41st Annual SES Technical Meeting, Lincoln, NE October 2004
“Human” Factor
The Need for Biocompatible Films
Orthopedic Implants
Contacts
Vascular Grafts
Pacemakers
Sutures
Stents
Catheters
Artificial Hips
Artificial Skin
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Polymer Thin Films
Control Over
Chemical Integrity
Thickness
Uniformity
Environment
Adhesion
Deposition Techniques
Aerosol / Spray Coatings
Dip Coatings
Spin Coatings
Thermal Evaporation
Electrospray
Laser-Based
• Pulsed Laser Deposition
• Matrix Assisted Method
Polymer
• PLGA
Characterization
• SEM
• FTIR
• NMR
• GPC
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Conventional Pulsed Laser Deposition
laser entry
heated substrate
(400 - 900°C)
target
Deposition of high Tc superconductors, oxides, metals.
Applied to several classes of polymer systems over the last 10
yrs. with limited success.
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Matrix Assisted Pulsed Laser Evaporation
“MAPLE: The Gentle Process”
The volatile solvent absorbs a large % of the laser pulse. Upon
heating, the solvent is ablated, entraining the organic molecule in
tow to the substrate, facilitating thin film growth.
UV laser pulse
polymer
solvent
frozen target
volatile solvent is
pumped away
41st Annual
SES Technical Meeting, Lincoln, NE October 2004
Substrate
Experimental Conditions
PLD
1) Target: solid polymer disk (100,000 MW, (75% LA, 25% GA:
PLGA 75/25, FDA approved)
2) Pump down to 10-6 Torr
3) Backfill to 100 mTorr Ar
4) Excimer laser – 248 nm, 25 ns, 5-10 Hz
MAPLE
1) Target: CHCl3** mixed with 1 wt. % PLGA
2) Vortex mixer: 20 minutes, flash freeze in liquid N2
3) Cold stage cooled to 120K
4) Pump down to 10-6 Torr
5) Backfill to 100 mTorr Ar, continuous flow, dynamic vacuum
**CHCl
has been a conventionally used solvent for MAPLE experiments due to it relative
high melting temperature of -63°C
3
41st Annual SES Technical Meeting, Lincoln, NE October 2004
SEM of PLD Deposited Films
(a) 0.20 J/cm2
100 nm (b) 0.38 J/cm2
1 µm (c) 0.58 J/cm2
(e) 1.0 J/cm2
(d) 0.77 J/cm2
1 µm
(g) 0.58 J/cm2, 10° Tilt
(f) 0.38 J/cm2, 10° Tilt
1 µm
(h) 0.77 J/cm2, 15° Tilt
1 µm
1 µm
(i) 1.0 J/cm2, 15° Tilt
1 µmSES Technical Meeting, Lincoln,1 NE
µmOctober 2004
41st Annual
1 µm
SEM of MAPLE Deposited Films
(a) 0.10 J/cm2
1 µm (b) 0.15 J/cm2
1 µm (c) 0.20 J/cm2
(d) 0.40 J/cm2
(e) 0.56 J/cm2
(f) 0.76 J/cm2
1 µm
1 µm
(g) 1.0 J/cm2
(h) 0.40 J/cm2
1 µm
1 µm
(i) 1.0 J/cm2
1 µmSES Technical Meeting, Lincoln,
100 nm
41st Annual
NE October 2004
100 nm
41st
Annual SES Technical Meeting, Lincoln, NE October 2004
1 µm
Fourier Transform Infrared Spectroscopy (FTIR)
1 0 0
P
L
G
A
7 5 / 2 5
N
a t i v e
8 0
Intensity
OH
6 0
C-H
bend
4 0
2 0
0
4 0 0 0
C-H
stretch
3 6 0 0
C=O
3 2 0 0
W
2 8 0 0
2 4 0 0
a v e n u m
2 0 0 0
b e r s
1 6 0 0
( c m
- 1
1 2 0 0
)
Probable Bond
Corresponding Peak Assignments
OH End group
3509.9 cm-1
C-H Stretch of CH3
3010 cm-1 and 2955 cm-1
C-H Stretch of CH2
2885 cm-1
C=O Stretch
1762.6 cm-1
C-O Stretch
1186-1089.6 cm-1*
C-H Bends
41st Annual SES Technical Meeting,
1450-850cm
Lincoln,-1*NE October 2004
8 0 0
FTIR Spectra - PLD
Intensity (au)
OH
4 0 0 0
C-H
Stretch
0 .2 0
J /c m
2
0 .7 7
J /c m
2
0 .3 8
J /c m
2
1 .0 5
J /c m
2
0 .5 8
J /c m
2
3 5 0 0
3 0 0 0
N a tiv e
2 5 0 0
2 0 0 0
C=O
1 5 0 0
C-H Bend
1 0 0 0
-1
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2004
5 0 0
FTIR Spectra - MAPLE
Intensity (au)
C-H
Stretch
OH
0 .1
J /c m
2
0 .4
J /c m
2
0 .7 7
J /c m
1 .0 J /c m
N a tiv e
4 0 0 0
3 5 0 0
41st
C-H Bend
C=O
2
2
3 0 0 0
2 5 0 0
2 0 0 0
?
1 5 0 0
1 0 0 0
- 1
W
a
v
e
n
u
m
b
e
r
s
(
c
m
Annual SES Technical Meeting, Lincoln, NE October )2004
5 0 0
Nuclear Magnetic Resonance (NMR)
GA
[ ][ ]
Deuterated
Chloroform CDCl3
O
3
O
O
Intensity (au)
3
7
6
4
CH3
2
CH3
O
O
OH
2
4
8
1
LA
1
5
4
P P M
3
2
1
Functional Group
Corresponding Peaks
Lactic acid CH
Multiplet at 5.2 ppm
Glycolic acid CH2
Multiplet at 4.8 ppm
Methyl groups of the D- and L- lactic acid
Overlapping doublets at1.55 ppm
Methyl group attached to the hydroxyl
1.25 ppm
endgroups
41st Annual SES Technical Meeting, Lincoln, NE October 2004
0
NMR Spectra - PLD
2
0 .7 7 0 J / c m
2
0 .3 8 8 J /c m
2
2
0 .5 8 1 J /c m
2
1 .0 1 5 J / c m
N a t iv e
Intensity (au)
0 .2 0 8 J /c m
6 .4
5 .6
4 .8
4
3 .2
2 .4
1 .6
0 .8
p m Lincoln, NE October 2004
41st Annual SES TechnicalpMeeting,
0
NMR Spectra - MAPLE
0 .2 J /c m
2
0 .7 6 J/cm
0 .4 J /c m
2
1 .0 J /c m
Intensity (au)
0 .5 6 J/cm
8
7
6
2
2
2
5
4
PPM
3
2
41st Annual SES Technical Meeting, Lincoln, NE October 2004
1
0
Summary FTIR, NMR
PLD and MAPLE deposited materials are similar to the
native signatures, additional decomposition peaks were
absent, particularly in the PLD spectra.
At lower fluences, MAPLE spectra become increasingly
difficult to obtain due to the lower amount of material
deposited.
41st Annual SES Technical Meeting, Lincoln, NE October 2004
GPC Trace - Native
Increasing MW
(Intensity)
Response (mV)
Concentration Detector
5 0
100 kDa
4 0
3 0
2 0
1 0
0
-1 0
-2 0
200 Da (monomer)
-3 0
1 0
1 5
2 0
(Time)
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( m L )2004
41st Annual SES Technical
Lincoln,
2 5
GPC Trace – PLD
0.4 J/cm2
50
100 kDa
Response (mV)
Concentration Detector
7.25 kDa
0
200 Da (monomer)
PLD
-5 0
10
15
20
R e te n
t i o n VLincoln,
o l u m eNE
( mOctober
L)
41st Annual SES Technical
Meeting,
2004
25
GPC Trace - MAPLE
0.4 J/cm2
200
(monomer)
Response (mV)
Concentration Detector
150
100
100 kDa
7.25 kDa
Native
26.5 kDa
MAPLE
50
0
-5 0
10
PLD
15
20
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( m L )2004
41st Annual SES Technical
Lincoln,
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Summary GPC
Significant degradation in terms of MW was observed for
both PLD and MAPLE deposited materials. This
amount of degradation was not expected with MAPLE,
therefore an analysis of the absorption and ablation
characteristics was conducted for a 1 wt. % polymer /
CHCl3 solution.
41st Annual SES Technical Meeting, Lincoln, NE October 2004
40
T Experimental
ra n s P u re
data points, pure chloroform
T Experimental
r a n s P L G Adata points, 1 wt.% PLGA
35
% Transmission
30
LP = 0.362 cm for pure CHCl3 solution
25
20
15
10
5
0
LP = 0.209 cm for the 1% PLGA / CHCl3 solution
0 .1
0 .2
0 .3
0 .4
T h i cMeeting,
k n eLincoln,
s s , zNE (October
c m )2004
41st Annual SES Technical
0 .5
Starting target
During ablation
target
laser
target holder / cold stage 1 mm
Target fracture @6,500 pulses
1 mm
remaining thickness
(d)
laser penetrated depths
cross section
1.2 cm
back
front surface
4 mm
1.85
µm2004
/ pulse
41st Annual SES Technical Meeting,
Lincoln,∼NE
October
4 mm
Conclusions
High Ablation Rate for MAPLE:
Weak absorption was measured for frozen CHCl3
a) Temperature models do not predict a large temperature increase
b) “Cold Laser Ablation or Spallation” models do not predict the required
stresses
c) Large “wicking” rings and a high density of particulate matter was
observed for all cases of MAPLE deposited films, supporting the theory of
large area spallation and subsequent solvent evaporation. Non-linear surface
effects, structural defects may be responsible.
MAPLE and PLD were compared for the first time in a direct study,
significant polymer fragmentation was shown to occur by both methods
In terms of the films: A broad range of MW were produced, with no clearly
defined new compounds: Promising for several medical apps such as drug
delivery, sensors, stents, and implants
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Future Work
(b)
(a)
30 nm
200 nm
fragmented regions
matrix material
(c)
200 nm
A combined experimental / computational approach will focus on the development
of improved matrices
and SES
the Technical
transport
of large
scaleNE
molecules.
41st Annual
Meeting,
Lincoln,
October 2004
Thanks for your attention - Questions
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Drug Delivery Systems
10 nm
100 nm
1 µm
10 µm
100 µm
1 mm
10 mm
Size
IM / SQ
Inhaled
Particle Size
IV
Nasal
Tablet
Granules
Oral
“Nanoparticles /
Microparticles”
Spray-coating
Encapsulation
Thicknesses
Spray-Freeze Drying
Super-Critical Fluids
NanocoatTM
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Polylactic co-glycolic acid (PLGA)
Random Co-Polymer
O
O
(
O
CH2 C
(
n
1
LA
[ ][ ]
O
)
Poly(lactic acid)
(PLA)
O
3
C
CH3
n
GA
1)
2)
3)
4)
CH
)
Poly(glycolic acid)
(PGA)
O
O
4
CH3
2
CH3
O
O
OH
Methyl group attached to the hydroxyl endgroups
Methyl groups of the D- and L- lactic acid
Glycolic acid
Lactic acid
Sample: 100,000 MW, (75%LA, 25% GA:PLGA 75/25)
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Brief, Non Encompassing Time Line for
Laser - Based Materials Processing
‘60
‘80
Discovery of
the Laser
Laser Interaction with
Materials, Primary
(Etching and Ablation,
Annealing, Chemistry)
1st Order
‘00
2nd Order
Laser Interaction with
Materials, Secondary
(Lithography, Film
Deposition)
Laser Interaction with Materials,
Secondary - Novel Matrix Methods:
Biological - Electronic -Organic
Materials Research
?
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Molecular Bond
C=O
C=C
O-H
C-H
N-H
C-O
C-C
S-H
C-N
Bond Dissociation Energy (eV)
7.5
6.4
4.8
4.3
4.1
3.6
3.6
3.5
3.0
Bond dissociation energies of molecular bonds common in
polymers. Italicized apply to this study.
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Typical Chemical Sensor Transducer
Frequency (Hz)
DMMP
Vapor On
a
Chemoselective
Coating
Vapor
Interdigitated
Electrodes
Frequency
250MHz
10KHz
Piezoelectric
Substrate
b
Vapor Off
shift
SAW Chemical Sensor
(Surface Acoustic Wave)
Time (sec) 20s
The MAPLE coated SAW gas sensor responds faster
than the spray coated sensor to dimethylmethylphosphonate.
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Conventional Laser Processing of PLGA Grown by
PLD : 1H-NMR
PLGA
GA
O
3
4
4
O
O
Deposited PLGA
4
3
]
CH3
2
5
CH3
O
1
LA
[ ][ ]
3
2
CH3
O
OH
1
O
2
or H2O ?
5
1
J.D. Talton, J.M. Fitz-Gerald, R.K. Singh, G. Hochhaus, “Nano-Thin Coatings for Improved Lung Targeting of Inhaled
Glucocorticoid Dry Powders: In-Vitro and In-Vivo Characteristics”, Respiratory Drug Delivery VII, pp. 67-74, 2000.
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Why Are New Methods Needed to
Process Polymer Thin Film Coatings?
• Electronic & Photonic Devices:
– Improved Quality Control and Performance
• Biological & Chemical Sensors:
– Optimized Kinetics
– Nanoscale Filtering
• Improved Drug Delivery:
– Biocompatibility
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Gel Permeation Chromatography (GPC)
•Mobile phase – Specimen
dissolved in liquid phase
(CHCl3)
• Stationary phase - porous
gel bed
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Experimental Setup
cold stage
laser pulse
Substrate
41st Annual SES Technical Meeting, Lincoln, NE October 2004
Future Work
(b)
(a)
30 nm
200 nm
fragmented regions
matrix material
(c)
200 nm
Fitz-Gerald et al., “Deposition of Nanotubes and Nanotube Composites using Matrix-Assisted Pulsed Laser
st Annual
SES617,
Technical
Meeting, Lincoln, NE October 2004
Deposition”, Mat. Res. 41
Soc.
Proc. Spring,
J2.3 (2000).