Using Rheology to Characterize Flow and Viscoelastic Properties of Hydrogels, Adhesives and Biopolymers
Tianhong Terri Chen PhD Senior Applications Scientist TA Instruments – Waters LLC
TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM Rheology: An Introduction
TAINSTRUMENTS.COM Rheology: An Introduction
Rheology: The study of the relationship between a stress and deformation
Deformation Solid F = F(x); F ≠ F(v) Purely Elastic
Most material Deformation + Flow Viscoelastic
Flow Liquid F = F(v); F ≠ F(x) Purely Viscous
Stress Stress = Modulus = Viscosity Strain Shear rate
TAINSTRUMENTS.COM 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.
TAINSTRUMENTS.COM Who Will Need Help with Rheology Analysis?
Food Personal Care Pharmaceutical
Polymers Adhesives & coating Automotive
Aerospace
Bio-medical devices Asphalt TAINSTRUMENTS.COM 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)
TAINSTRUMENTS.COM Rotational Rheometers at TA
ARES G2 DHR
Controlled Strain Controlled Stress Dual Head Single Head SMT CMT
TAINSTRUMENTS.COM Geometry Options
Concentric Cone and Parallel Torsion Cylinders Plate Plate Rectangular
Very Low Very Low Very Low Solids to Medium to High Viscosity Viscosity Viscosity to Soft Solids Water to Steel
TAINSTRUMENTS.COM DMAs from TA Instruments
RSA G2 Q800 ARES G2 and DHR
Controlled Strain Controlled Stress DMA mode SMT CMT (oscillation)
TAINSTRUMENTS.COM DMA Clamps
Submersible Submersible S/D Cantilever Tension-Film Shear-Sandwich Compression 3 Pt Bend
Submersible 3-Point Bending Tension-Fiber Compression Tension
TAINSTRUMENTS.COM ElectroForce Load Frames
ElectroForce 3300 ElectroForce 3510 ElectroForce 3500 Floor Standing (7500 N) (15000 N) ElectroForce 3300 (3000 N) (3000 N) ElectroForce 3200 (450 N) ElectroForce 5500 ElectroForce 3100 (200 N) (22 N)
Frequency Forces to Interchangeable to 300 Hz 15kN Fixtures
TAINSTRUMENTS.COM Common Rheological Experimental Methods
TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM Flow Behaviors
TAINSTRUMENTS.COM Information from a Flow Curve
What shear rate? 4) Chewing, swallowing 5) Dip coating 1) Sedimentation 6) Mixing, stirring 2) Leveling, Sagging 7) Pipe flow 3) Draining under gravity η
log 8) Spraying and brushing 9) Rubbing 10) Milling pigments 11) High Speed coating
4 5 6 8 9 1 2 3 7 10 11
1.00E-5 1.00E-4 1.00E-3 0.0100 0.100 1.00 10.00 100.00 1000.00 1.00E4 1.00E5 1.00E6
shear rate (1/s)
TAINSTRUMENTS.COM Dynamic Oscillatory Tests
Phase angle δ Strain, ε
Stress, σ*
Dynamic stress applied sinusoidally User-defined Stress or Strain amplitude and frequency
TAINSTRUMENTS.COM Viscoelastic Parameters
The Modulus: Measure of materials overall ∗ = ∗ resistance to deformation. The Elastic (Storage) Modulus: Measure of ∗ elasticity of material. The ability of the G = cos δ material to store energy.
The Viscous (loss) Modulus: ∗ G" = sin δ The ability of the material to dissipate energy. Energy lost as heat. Tan delta (phase angle): " tan δ = Measure of material damping - such as vibration or sound damping. G* The triangle relationship G"
Phase angle δ
G' TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM Rheology Applications in Biopolymers & Biomedical Materials
TAINSTRUMENTS.COM Purpose of a Rheological Measurement
Three main reasons for rheological testing:
• Characterization Structure-property relationship. MW, MWD, branching, state of flocculation, etc.
• Process performance Formulation stability, processing temperatures, extrusion, blow molding, pumping, leveling, etc.
• End product properties Mechanical strength, glass transition and sub-ambient transition temperatures, dimensional stability, settling stability, etc.
TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM 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.
TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM Gels: Gelatin Gelation vs. Temperature
Thermal reversible gelatin gels: o Measure gelation and gel melt
TAINSTRUMENTS.COM Gelatin Gel Strength at Different Concentration
• A dynamic frequency sweep test can be used to compare gel strength at applications temperature
TAINSTRUMENTS.COM Gelatin/Chitosan Conjugation
• Use enzymatic approach to covalently graft gelatin to chitosan
• The conjugate exhibits interesting Tyrosine mechanical properties • Applications as biomedical adhesives
Chen et al. Biopolymers, Vol. 64, 292-302 (2002)
TAINSTRUMENTS.COM Vesicle-Biopolymer Gels
• 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 HM-Chitosan behavior and has potential applications in biomedical control release
Chen T; Raghavan SR et al, Langmuir, 21, 26-33 (2005)
TAINSTRUMENTS.COM Contact Lens Visco-elasticity
• Compare frequency dependency of contact lens elasticity
0.3500 " t = 0.3000 Vendor A
0.2500
0.2000 Vendor B
tan(delta) 0.1500
0.1000
0.05000
0 1.000 10.00 100.0 ang. frequency (rad/s)
TAINSTRUMENTS.COM Creams/Lotions: Stability Testing
Stability, phase separation of a cosmetic cream
1E+06
l G' emulsion Ap G'' emulsion A l G' emulsion Bp G'' emulsion B 1E+05
l l l l l l l l l l l l l 1E+04 l p p p lp p ' ' ' ' l' 'p 'p 'p 'p 'p 'p l l
Moduli [Pa] G'' & G' l l l l 1E+03 0 1 2 3 4 5 6 7 8 910 strain [%]
TAINSTRUMENTS.COM High Temperature Performance of Lotions
A: Hydrating Lotion B: UV Protection C: Generic Brand
o 10 3 G‘ for A decreases at 37 C G‘ for B withstands higher temperature =>used at 10 2 2 higher temperature
hydrating beauty lotion δ same lotion with UV protection conditions (beach) generic hydrating lotion 1 10 G‘ for lotion C increases
Loss tan before dropping; tan δ decreases => phase ModulusG' [Pa] 0 10 0 separation for lotion C Tan δ for A & B increases above 37 oC=> wax crystals 0 10 20 30 40 50 60 melt and lower the modulus Temperature T [°C]
Ming L. Yao; Jayesh C. Patel Appl. Rheol. 11 ,2,83 (2001)
TAINSTRUMENTS.COM Low Temperature Performance of Lotions
0.8
7 6 10 w/o emulsion 10 o/w emulsion: G' G' 10 6 G" 0.6 G" 5 tand δ 10 10 5
0.4 δ 10 4 tan 10 4 3 Modulus [Pa] G' 10 0.2 Modulus G', G" [Pa] Modulus G" G',
Modulus G’, G” [Pa] G” G’, Modulus 2 10 3 10 -8 oC 0.0 -30 -20 -10 0 10 20 30 -100 -80 -60 -40 -20 0 20 40 60 80 100 Temperature T [ oC] Temperature T [ oC]
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
TAINSTRUMENTS.COM Emulsion Temperature Stability
• Cycle temperature to evaluate temperature stability of emulsions
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
TAINSTRUMENTS.COM Lotions: Coefficient of Friction
Application window
37°C, 3 N load Transpore
TAINSTRUMENTS.COM Biomedical Adhesives
• 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
35 TAINSTRUMENTS.COM Bio-adhesives Test Methodologies
TAINSTRUMENTS.COM Adhesive Tack Testing
• Experimental: 8mm parallel plate, Axial tensile at 0.1mm/sec
Crosslinked PSA: Non-Crosslinked PSA: Adhesive failure Cohesive failure
TAINSTRUMENTS.COM Adhesive 180 Degree Peel Test
• The SER geometry on a rheometer can perform peel test at 180 degree angel.
http://www.xpansioninstruments.com/results_peel.htm
TAINSTRUMENTS.COM Adhesive Temperature Ramp
• Most popular test in adhesive industry • The measurement results correlate to the performance of a PSA with temperature
• Glass transition: Tg = 16.3 °C
• G crossover: Tx = 75.9 °C
• Dahlquist temperature: Td = 11.6 °C
• Plateau modulus G’p = 7694 Pa
TAINSTRUMENTS.COM Adhesive: Tack and Peel Performance
• A dynamic frequency sweep test results can correlates to tack and peel performance
Tack and Peel performance of a PSA
good tack and peel Bad tack and peel
10 4
peel
10 3
Storage Modulus [Pa] G' Modulus Storage tack
0.1 1 10 Frequency ω [rad/s]
TAINSTRUMENTS.COM Dental Adhesive UV Curing
• Dental materials cure under blue light
1.000E9
1.000E8
1.000E7
1.000E6
|G*| (Pa) 1.000E5 Formulation #1 10000 Formulation #2 Formulation #3 1000 Formulation #4 Formulation #5
100.0 10.000 20.000 30.000 40.000 50.000 60.000 70.000 80.000 time (s)
TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM Gelatin Capsule: Mechanical Strength vs. Temperature and Humidity
• A dynamic temperature or humidity ramp experiment can help evaluate the mechanical properties (stability) of gelatin capsules at different storage conditions (temperature and humidity).
5000 100 25°C
4000 400 80 50°C 37°C 3000 300 60
2000 200 40 Loss Modulus (MPa) Relative Humidity (%) Storage Modulus (MPa)
1000 100 20 ––––––– T25C-RAMP RH.001 – – – – T37C-RAMP RH.001 ––––– · T50C-RAMP RH.001 0 0 30 40 50 60 70 80 90 Time (min) Universal V4.7A TA Instruments TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM HPMC Gelation Mechanism
• Thermal reversible gel • Transition from intra-molecular interaction to inter-molecular interaction
10000 10000 HPMC Temp Ramp Capsule manufacturing process – a hot pin dipped 1000 1000 into a cold solution
Gelation T = 60.5 °C (Pa) '' G G': 8.190 Pa 100.0 100.0 G' (Pa)
10.00 10.00
1.000 1.000 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0 temperature (°C)
TAINSTRUMENTS.COM Polymers – Medical Devices
• Polymers are used as medical devices such as hips and knees joints, sutures, stents, and facial prostheses etc.
• Rheology helps to guide Application Polymer Used process conditions and Knee, Hip, & Shoulder Ultrahigh molecular weight evaluate end product Joints polyethylene (UHMWPE) Finger Joints Silicone performance 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
47 TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM 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.
TAINSTRUMENTS.COM Idealized Flow Curve – Polymer Melts
Power Law Region
First Newtonian Plateau
η0 = Zero Shear Viscosity 3.4 η0 = K x MW Extend Range ηη with Time- Temperature log log Superposition (TTS) Measure in Flow Mode & Cox-Merz
Extend Range Second Newtonian with Oscillation Plateau & Cox-Merz
Molecular Structure Compression Molding Extrusion Blow and Injection Molding
1.00E-5 1.00E-4 1.00E-3 0.0100 0.100 1.00 10.00 100.00 1000.00 1.00E4 1.00E5 shear rate (1/s)
TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM PLA Melt Temp Ramp Test on a Rheometer
• A dynamic temperature ramp test on rheometer can help to investigate appropriate extrusion temperature and also cooling conditions
10 8
10 7
10 6 Heating 10 5
10 4
10 3 Cooling 10 2 Heating
10 1 80 100 120 140 160 180 200 Temperature (°C)
TAINSTRUMENTS.COM PLA End Product Performance-Fast Cooling
• PLA fast cooling after extrusion
TAINSTRUMENTS.COM PLA End Product Performance-Slow Cooling
• PLA slow cooling after extrusion
TAINSTRUMENTS.COM PLA – Compare Different Process Conditions
10 10 3.5
PLA Slow Cooling PLA Fast Cooling 3.0
10 9 2.5
2.0
10 8
1.5
1.0 10 7
0.5
10 6 0.0 20 40 60 80 100 120 140 160 Temperature (°C)
TAINSTRUMENTS.COM 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
TAINSTRUMENTS.COM Agenda
•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
57 TAINSTRUMENTS.COM Thank you for your attention!
TAINSTRUMENTS.COM