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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


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


Rheology: An Introduction


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


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.


Who Will Need Help with Rheology Analysis?

Food PharmaceuticalPersonal Care

Adhesives & coating

Polymers

AsphaltBio-medical devices

Automotive

Aerospace


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)


Rotational Rheometers at TA

Controlled Strain

Dual Head

SMT

ARES G2 DHR

Controlled Stress

Single Head

CMT


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


DMAs from TA Instruments

Controlled Strain

SMT

RSA G2 Q800

Controlled Stress

CMT

ARES G2

and DHR

DMA mode(oscillation)


DMA Clamps

S/D Cantilever

3-Point Bending

Tension-Film

Tension-Fiber

Shear-Sandwich

Compression

Submersible

Compression

Submersible

Tension

Submersible

3 Pt Bend


ElectroForce Load Frames

ElectroForce 3100 (22 N)


ElectroForce 3200

(450 N)


ElectroForce 3300

Floor Standing

(3000 N)


ElectroForce 3500

(15000 N)

Frequency

to 300 HzForces to

15kNInterchangeable

Fixtures


Common Rheological

Experimental Methods


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


Flow Behaviors


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


Dynamic stress applied sinusoidally

User-defined Stress or Strain amplitude and frequency

Phase angle δ

Strain, ε

Stress, σ*

Dynamic Oscillatory Tests


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


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


Rheology Applications in

Biopolymers & Biomedical Materials


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


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


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.


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


Gels: Gelatin Gelation vs. Temperature

� Thermal reversible gelatin gels:

o Measure gelation and gel melt


Gelatin Gel Strength at Different Concentration

• A dynamic frequency sweep test can be used to compare

gel strength at applications temperature


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


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


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!"# =$"

$%


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


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


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]


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


Lotions: Coefficient of Friction

37°C, 3 N loadTranspore

Application

window


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


Bio-adhesives Test Methodologies


Adhesive Tack Testing

Crosslinked PSA:

Adhesive failure

Non-Crosslinked PSA:

Cohesive failure

• Experimental:

8mm parallel plate, Axial tensile at 0.1mm/sec


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.


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


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]


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


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


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


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


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


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


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


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


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.


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


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


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


PLA End Product Performance-Fast Cooling

• PLA fast cooling after extrusion


PLA End Product Performance-Slow Cooling

• PLA slow cooling after extrusion


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


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


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


Thank you for your attention!

using rheology to characterize flow and viscoelastic ... · using rheology to characterize flow and...

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