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Using Rheology to Characterize Flow and
Viscoelastic Properties of Hydrogels, Adhesives
and Biopolymers
Tianhong Terri Chen PhD
Senior Applications Scientist
TA Instruments – Waters LLC
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Outline
� Basics in Rheology Theory
� TA Instruments Rheometers and DMAs
� Instrumentation
� Test methodologies
� Rheological Applications in Biopolymer and Biomedical Materials
� Hydrogels and creams
� Adhesives
� Drug capsules
� Polymers for medical devices
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Rheology: An Introduction
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Rheology: An Introduction
Rheology: The study of the relationship between a stress and deformation
ModulusStrain
Stress= Viscosity
rateShear
Stress=
F = F(x); F ≠ F(v)
Deformation
Flow
F = F(v); F ≠ F(x)
Purely Elastic
Purely Viscous
ViscoelasticDeformation + Flow
Solid
Most material
Liquid
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What does a Rheometer do?
� Rheometer – an instrument that measures both viscosity
and viscoelasticity of fluids, semi-solids and solids
� It can provide information about the material’s:
� Viscosity - defined as a material’s resistance to flow
deformation and is a function of shear rate or stress, with
time and temperature dependence
� Viscoelasticity – is a property of a material that exhibits
both viscous and elastic character. Measurements of
G’, G”, tan δ with respect to time, temperature,
frequency and stress/strain are important for
characterization.
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Who Will Need Help with Rheology Analysis?
Food PharmaceuticalPersonal Care
Adhesives & coating
Polymers
AsphaltBio-medical devices
Automotive
Aerospace
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TA Instruments Rheometers and DMAs
� TA Rotational Rheometers
� ARES-G2 and ARES (Strain Control – SMT)
� DHR or AR (Stress Control – CMT)
� TA DMAs
� RSA-G2 and RSA (Strain Control – SMT)
� DMA Q800 (Stress Control – CMT)
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Rotational Rheometers at TA
Controlled Strain
Dual Head
SMT
ARES G2 DHR
Controlled Stress
Single Head
CMT
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Geometry Options
ParallelPlate
Cone andPlate
ConcentricCylinders
TorsionRectangular
Very Low
to Medium
Viscosity
Very Low
to High
Viscosity
Very Low
Viscosity
to Soft Solids
Solids
Water to Steel
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DMAs from TA Instruments
Controlled Strain
SMT
RSA G2 Q800
Controlled Stress
CMT
ARES G2
and DHR
DMA mode(oscillation)
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DMA Clamps
S/D Cantilever
3-Point Bending
Tension-Film
Tension-Fiber
Shear-Sandwich
Compression
Submersible
Compression
Submersible
Tension
Submersible
3 Pt Bend
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ElectroForce Load Frames
ElectroForce 3100 (22 N)
ElectroForce 5500 (200 N)
ElectroForce 3200
(450 N)
ElectroForce 3300 (3000 N)
ElectroForce 3300
Floor Standing
(3000 N)
ElectroForce 3510 (7500 N)
ElectroForce 3500
(15000 N)
Frequency
to 300 HzForces to
15kNInterchangeable
Fixtures
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Common Rheological
Experimental Methods
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Flow Experiments
� What flow measures
o Viscosity
� “lack of slipperiness,” resistance to flow
� The viscosity of water at room temperature is 1cP
�Type of flow measurements on rheometer
o Viscosity vs. time
� Viscosity at single shear rate/stress
� Time dependence (Thixotropy or Rheopexy)
o Viscosity vs. shear stress or rate
� Newtonian
� Shear thinning, shear thickening,
� Yield stress
o Viscosity vs. temperature
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Flow Behaviors
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Information from a Flow Curve
1
1) Sedimentation2) Leveling, Sagging3) Draining under gravity
2 3
6
5
8 9
1.001.00E-5 1.00E-4 1.00E-3 0.0100 0.100
shear rate (1/s)
10.00 100.00 1000.00 1.00E4 1.00E5
log
η
1.00E6
117
4
10
What shear rate?
8) Spraying and brushing9) Rubbing10) Milling pigments 11) High Speed coating
4) Chewing, swallowing5) Dip coating6) Mixing, stirring7) Pipe flow
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Dynamic stress applied sinusoidally
User-defined Stress or Strain amplitude and frequency
Phase angle δ
Strain, ε
Stress, σ*
Dynamic Oscillatory Tests
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Viscoelastic Parameters
The Elastic (Storage) Modulus: Measure of elasticity of material. The ability of the material to store energy.
The Viscous (loss) Modulus:The ability of the material to dissipate energy. Energy lost as heat.
The Modulus: Measure of materials overall resistance to deformation.
Tan delta (phase angle):Measure of material damping - such as vibration or sound damping.
G�=
����∗
����� cos δ
G"=
����∗
����� sin δ
�∗=
������∗
������
tan δ = "
�
Phase angle δ
G*
G'
G"The triangle relationship
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Understanding Oscillation Experiments
� What oscillation measures?
oViscoelastic properties (G’/E’, G”/E”, tan δ)
� Approach to Oscillation Experimentation
oStress and Strain Sweep
• Measure linear viscoelastic region
• Yield stress, stability
oTime Sweep
• Stability and structure recovery
• Curing
o Frequency Sweep
• Measure polymer relaxation
• Compare viscoelasticity of different formulations
oTemperature Ramp
• Measure glass transition,
• Temperature operation range of a material
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Rheology Applications in
Biopolymers & Biomedical Materials
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Three main reasons for rheological testing:
• CharacterizationStructure-property relationship. MW, MWD, branching, state of flocculation, etc.
• Process performanceFormulation stability, processing temperatures, extrusion, blow molding, pumping, leveling, etc.
• End product propertiesMechanical strength, glass transition and sub-ambient transition temperatures, dimensional stability, settling stability, etc.
Purpose of a Rheological Measurement
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Hydrogels and Creams
• Hydrogels and creams are soft matters that contain high level of liquids such as water or oil
• Hydrogels and creams are used in a wide variety of applications including tissue engineering, wound patch, drug delivery, contact lenses and superabsorbent materials
• Rheology can provide key information on gel formation and gel strength on different formulations
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Natural Polymer: Hyaluronic Acid
• Hyaluronic acid is a natural polysaccharide, which is commonly used in pharmaceutical, biomedical and personal care
• Rheology can evaluate the visco-elastic properties as function of concentration, ionic strength, Mw, degree of crosslinking, formulations etc.
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Hyaluronic Acid Gels:
• Hyaluronic acid gels are used as lubricating agent during abdominal surgeries to prevent adhesion and also for join lubrication, wound healing etc.
• Rheology can monitor HA gelation and evaluate the gel strength
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Gels: Gelatin Gelation vs. Temperature
� Thermal reversible gelatin gels:
o Measure gelation and gel melt
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Gelatin Gel Strength at Different Concentration
• A dynamic frequency sweep test can be used to compare
gel strength at applications temperature
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Gelatin/Chitosan Conjugation
• Use enzymatic approach to
covalently graft gelatin to chitosan
• The conjugate exhibits interesting
mechanical properties
• Applications as biomedical
adhesives
Chen et al. Biopolymers, Vol. 64, 292-302 (2002)
Tyrosine
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Vesicle-Biopolymer Gels
Chen T; Raghavan SR et al, Langmuir, 21, 26-33 (2005)
• Attach n-dodecyl tails to Chitosan
backbone to obtain an associating
biopolymer (HM-Chitosan)
• HM-Chitosan mixed with surfactant
vesicle solution leads to a gel formation
• This hydrogel showed strong elasticity
behavior and has potential applications
in biomedical control release
HM-Chitosan
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Contact Lens Visco-elasticity
1.000 10.00 100.0ang. frequency (rad/s)
0
0.05000
0.1000
0.1500
0.2000
0.2500
0.3000
0.3500
tan(d
elta)
Vendor A
Vendor B
• Compare frequency dependency of contact lens elasticity
t!"# =$"
$%
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Creams/Lotions: Stability Testing
' '' ' ' ' ' ' ' ' '
l
l
ll
ll
ll
l l l
pp
p p p p p p p p p
l
l
l l l l l l l ll
0 1 2 3 4 5 6 7 8 9 10
strain [%]
1E+03
1E+04
1E+05
1E+06
Mo
du
li G
' & G
'' [P
a]
G' emulsion A G'' emulsion A
G' emulsion B G'' emulsion B
l p
l p
Stability, phase separation of a cosmetic cream
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High Temperature Performance of Lotions
0 10 20 30 40 50 60
100
101
102
103
0
2
hydrating beauty lotion
same lotion with UV protection
generic hydrating lotion
Mod
ulu
s G
' [P
a]
Temperature T [°C]
Lo
ss tan
δ
� G‘ for A decreases at 37oC
� G‘ for B withstands higher
temperature =>used at
higher temperature
conditions (beach)
� G‘ for lotion C increases
before dropping; tan δdecreases => phase
separation for lotion C
� Tan δ for A & B increases
above 37oC=> wax crystals
melt and lower the modulus
Ming L. Yao; Jayesh C. Patel Appl. Rheol. 11,2,83 (2001)
A: Hydrating Lotion B: UV Protection C: Generic Brand
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Low Temperature Performance of Lotions
-30 -20 -10 0 10 20 30
103
104
105
106
o/w emulsion:
G'
G"
-8oC
Mo
du
lus G
' [P
a]
Temperature T [oC]
-100 -80 -60 -40 -20 0 20 40 60 80 100
102
103
104
105
106
107
0.0
0.2
0.4
0.6
0.8
w/o emulsion
G'
G"
Mo
du
lus G
', G
" [P
a]
Temperature T [oC]
tand δ
tan
δ
� In an o/w emulsion the freezing point of water is depressed due to the dispersed oil phase. Cooling below the freezing point has a major effect on temperature stability
� In an w/o emulsion, the dispersed water droplets freeze, but not the matrix. These emulsions do not have a sharp freezing point
R.Brummer Rheology essentials of Cosmetics Springer ISBN: 3-540-25553-2
Modulu
s G
’, G
” [P
a]
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Emulsion Temperature Stability
V. André, N. Willenbacher, H. Debus, L. Börger, P. Fernandez, T. Frechen, J. Rieger. Prediction of Emulsion Stability:
Facts and Myth . Cosmetics and Toiletries Manufacture Worldwide
• Cycle temperature to evaluate temperature stability of emulsions
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Lotions: Coefficient of Friction
37°C, 3 N loadTranspore
Application
window
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Biomedical Adhesives
35
• Adhesives are used in biomedical device assembly; hard
tissue or soft tissue attachments (e.g. dentistry or wound
closure)
• Rheology helps to guide adhesive process
• Rheology measurements can correlate to the tack and
peel performance of the finial products
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Bio-adhesives Test Methodologies
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Adhesive Tack Testing
Crosslinked PSA:
Adhesive failure
Non-Crosslinked PSA:
Cohesive failure
• Experimental:
8mm parallel plate, Axial tensile at 0.1mm/sec
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Adhesive 180 Degree Peel Test
http://www.xpansioninstruments.com/results_peel.htm
• The SER geometry on a rheometer can
perform peel test at 180 degree angel.
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Adhesive Temperature Ramp
• Glass transition:
Tg = 16.3°C
• G crossover:
Tx = 75.9°C
• Dahlquist temperature:
Td = 11.6°C
• Plateau modulus
G’p = 7694 Pa
• Most popular test in adhesive industry
• The measurement results correlate to the performance of a
PSA with temperature
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Adhesive: Tack and Peel Performance
• A dynamic frequency sweep test results can correlates to tack and peel
performance
0.1 1 10
103
104
Tack and Peel performance of a PSA
peel
tack
good tack and peel
Bad tack and peel
Sto
rage M
odulu
s G
' [P
a]
Frequency ω [rad/s]
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Dental Adhesive UV Curing
10.000 20.000 30.000 40.000 50.000 60.000 70.000 80.000time (s)
100.0
1000
10000
1.000E5
1.000E6
1.000E7
1.000E8
1.000E9
|G*|
(P
a)
Formulation #1Formulation #2Formulation #3Formulation #4Formulation #5
• Dental materials cure under blue light
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Adhesive Curing Shrinkage
• Adhesive curing shrinkage will cause fractures in process
• Using rheometer + UV curing accessory, we can quantitatively monitor the shrinking force during curing or the dimension shrinkage
Monitor force buildup Monitor dimension/gap change
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Drug Capsules
•Drug capsules are typically made from gelatin or polysaccharide such as (HPMC)
•Rheology and DMA can help to investigate the optimum capsule process conditions and also evaluate the capsule properties with a controlled temperature and humidity
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Gelatin Capsule: Mechanical Strength vs. Temperature and Humidity
100
200
300
400
Lo
ss M
od
ulu
s (
MP
a)
0
20
40
60
80
100
Re
lative
Hu
mid
ity (
%)
0
1000
2000
3000
4000
5000
Sto
rag
e M
od
ulu
s (
MP
a)
30 40 50 60 70 80 90
Time (min)
T25C-RAMP RH.001––––––– T37C-RAMP RH.001– – – – T50C-RAMP RH.001––––– ·
Universal V4.7A TA Instruments
• A dynamic temperature or humidity ramp experiment can help evaluate the mechanical properties (stability) of gelatin capsules at different storage conditions (temperature and humidity).
25°C
50°C
37°C
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Water Soluble Cellulose - HPMC
• Hydroxypropyl methylcellulose (HPMC)
• Soluble in cold water, insoluble in hot water. Gelation temperature and gel strength depending on the ratio of HP/MC and degree of substitution
• Cellulose based drug capsules
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HPMC Gelation Mechanism
20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0temperature (°C)
1.000
10.00
100.0
1000
10000
G'
(Pa
)
1.000
10.00
100.0
1000
10000
G'' (P
a)
HPMC Temp Ramp
Gelation T = 60.5 °CG': 8.190 Pa
• Thermal reversible gel
• Transition from intra-molecular interaction to inter-molecular interaction
Capsule manufacturing
process – a hot pin dipped
into a cold solution
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Polymers – Medical Devices
47
• Polymers are used as medical devices such as hips and
knees joints, sutures, stents, and facial prostheses etc.
Application Polymer Used
Knee, Hip, & Shoulder Joints
Ultrahigh molecular weight polyethylene (UHMWPE)
Finger Joints Silicone
Sutures Polylactic and Polyglycolic acid, Nylon
Tracheal Tubes Silicone, Acrylic, Nylon
Heart Pacemaker Acetal, Polyethylene, Polyurethane
Blood Vessels Polyester, PVC, Polytetrafluoroethylene,
Gastrointestinal Segments Nylon, PVC, Silicones
Facial Prostheses Polydimethyl siloxane, Polyurethane, PVC
Bone Cement Polymethyl methacrylate
• Rheology helps to guide
process conditions and
evaluate end product
performance
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Polylactic Acid (PLA)
• Polylactic acid (PLA) and its composite materials are FDA approved synthetic degradable polymers. It shows many good characteristic features:
� Biocompatibility
� Biodegradability
� Good process ability
� Low cost
• PLA has been widely used in many biomedical applications such as
� Orthopedics
� Drug carriers
� Stents
� Tissue engineering
� Antimicrobial agents
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What Rheology Can Help?
• Rheology helps to investigate processing conditions (e.g.
temperature and shear). Polymer processing technologies
including extrusion, injection molding and blow molding.
• Rheology provides quantitative evaluation on the end unit
performance of PLA based products. Such as influence of
Mw, plasticizers, stabilizers, pigments and fillers etc.
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Idealized Flow Curve – Polymer Melts
1.001.00E-5 1.00E-4 1.00E-3 0.0100 0.100
shear rate (1/s)
10.00 100.00 1000.00 1.00E4 1.00E5
log
η
Molecular Structure Compression Molding Extrusion Blow and Injection Molding
η0 = Zero Shear Viscosity
η0 = K x MW 3.4
Measure in Flow Mode
Extend Rangewith Oscillation
& Cox-Merz
Extend Range
with Time-Temperature
Superposition (TTS)
& Cox-Merz
First Newtonian Plateau
Second Newtonian Plateau
Power Law Region
1.001.00E-5 1.00E-4 1.00E-3 0.0100 0.100
shear rate (1/s)
10.00 100.00 1000.00 1.00E4 1.00E5
log
η
Molecular Structure Compression Molding Extrusion Blow and Injection Molding
η0 = Zero Shear Viscosity
η0 = K x MW 3.4
Measure in Flow Mode
Extend Rangewith Oscillation
& Cox-Merz
Extend Range
with Time-Temperature
Superposition (TTS)
& Cox-Merz
First Newtonian Plateau
Second Newtonian Plateau
Power Law Region
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PLA Melt Flow Processing Temperature
• DSC Indicates PLA melt at 170°C. The extrusion process temperature needs to
be greater than Tm (melt) but lower than Td (decomposition).
• After melt, extrusion temperature may need to be adjusted to reach ideal shear
viscosity
R. Al-Itry et al. / Polymer Degradation and Stability 97 (2012) 1898e1914
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PLA Melt Temp Ramp Test on a Rheometer
20080 100 120 140 160 180
Temperature (°C)
10 1
10 2
10 3
10 4
10 5
10 6
10 7
10 8
Cooling
Heating
Heating
• A dynamic temperature ramp test on rheometer can help to investigate
appropriate extrusion temperature and also cooling conditions
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PLA End Product Performance-Fast Cooling
• PLA fast cooling after extrusion
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PLA End Product Performance-Slow Cooling
• PLA slow cooling after extrusion
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PLA – Compare Different Process Conditions
16020 40 60 80 100 120 140
Temperature (°C)
10 6
10 7
10 8
10 9
10 10 3.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0PLA Slow Cooling
PLA Fast Cooling
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Summary
• Rheology is a powerful tool for investigating viscosity and viscoelastic properties of biopolymer materials and biomedical devices
• Materials evaluated by rheological techniques can be either liquids, semi-solids, gels, or solids. The viscoelastic properties can be monitored as a function of time, temperature, frequency, shear rate and shear stress
• The rheological measurement information can be used for
� Basic research and product development
� Trouble shooting manufacturing problems
� General QC analysis, distinguish batch to batch variation
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Agenda
57
•9 - 10:15am: Thermal analysis and stability of biomaterials
•10:15-10:30am: Break
•10:30-noon: Using rheology to characterize flow and
viscoelastic properties of hydrogels, adhesives and biopolymers
•12-1pm: Lunch
•1-2:15pm: Mechanical testing of medical devices
•2:15-2:30 - break
•2:30-3:15pm: Mechanical testing of engineered tissues and
biomaterials
•3:15-4pm – Q&A with TA Instruments Applications Engineers
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Thank you for your attention!