Effect of Thermal Properties on Heat Transfer in Cryopreservation and Cryosurgery

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Effect of Thermal Properties on Heat Transfer in
Cryopreservation and Cryosurgery

• Bumsoo Han and John C. Bischof
• Department of Mechanical Engineering
• University of Minnesota
• ASME International Mechanical Engineering
  Congress Exposition
• November 19, 2002, New Orleans, Louisiana

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Heat and Mass Transfer during Cryopreservation
and/or Cryosurgery

• Heat and mass transfer with phase change
• Governing equation
• where
• ? If the thermal properties of biological systems
  are known at subzero temperature, heat and mass
  transfer problems can be predicted by solving the
  equation.

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Thermal Properties of Biomaterials

• From Bald and Fraser (1982), Bowman et al.
  (1975), Diller et al. (1999) and ASHRAE
  Refrigeration Handbook (2000)

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Objectives of Thermal Engineering Side

• ULTIMATE GOAL
• Development of reliable freezing/thawing
  protocols
• for cryopreservation/cryosurgery applications
• Construct thermal property database of
  biomaterials at subzero temperature
• Developing numerical models as prediction tools
  to improve cryopreservation/ cryosurgery
  protocols

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Methods

• DSC and Cryomicroscopy
• ? Specific and latent heat, Phase change
  behavior
• Pulse-Decay Method
• ? Thermal conductivity
• Numerical analysis
• ? Thermal history and phase change interface
• movement

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Specific HeatPhosphate Buffered Saline (PBS) and
PBSCPA
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DSC Thermogram and Cryomicroscopy (5xPBS)
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Latent Heat of Various Solutions
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Pulse-Decay MethodTheoretical Background

• A thermal conductivity measurement technique by
  monitoring the heat dissipation (i.e. temperature
  decay) of a thermistor heated with known electric
  power
• 1-D transient conduction with a point heat source
  
• Analytic temperature variation
• where P is electric power and tp is heating
  duration.

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Schematic Diagram of Pulse-Decay Setup
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Thermal Conductivity of Various Solutions
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Constant vs Variable Thermal Properties Thermal
History of Cryopreservation
Freezing interface Temperature history
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Summary and Conclusions

• Measurement of specific heat Cp
• Solutions w/o CPA ( gt-150ºC) Water/ice
• Tissues ( gt-40ºC) lt Water/ice
• Measurement of latent heat L and phase change
• Freezing process Thermodynamic non-equilibrium
  process even though pre-nucleation of water
• Thawing process Close to thermodynamic
  equilibrium
• Eutectic formation of PBS disappears when a CPA
  is added.
• Measurement of thermal conductivity k
• Solutions ( gt-40ºC) gt Water/ice
• Tissues ( gt-40ºC) lt Water/ice

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Future Research

• Application of the developed techniques to
  native/artificial tissues
• Development of numerical (or theoretical) model
  to simulate non-equilibrium eutectic phase change
  during freezing and equilibrium eutectic phase
  change during thawing
• Investigation of the effect of microscale
  crystal structure on thermal conductivity

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Acknowledgements

• NIH 5R29CA75284-05
• NSF BES 9703326

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Cryomicroscopy Images1xPBS 0.1M Glycerol
(a) Nucleation (b) Ice crystal growth
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Cryomicroscopy Images1xPBS 5M Glycerol
(a) Nucleation (b) Ice crystal growth
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Data Processing
Converted Thermistor Resistance
Converted Thermistor Temperature
Measured Voltage
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Thermal Properties of Biomaterials

• Latent heat - L (J/g), Phase change behavior
• Specific heat - Cp
• Thermal conductivity -k (W/m?K)
• Water is considered as an extreme case.
• From Bald and Fraser (1982), Bowman et al.
  (1975), Diller et al. (1999)

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Applications of Cryobiology

• Cryopreservation
• Banking of cells and tissues in frozen state
  prior to thawing and use
• Objective Freezing the cells and tissues
  without freezing injuries

• Cryosurgery
• Freezing to destroy unwanted or malignant
  tissues such as tumors in the body
• Objective Freezing the cells and tissues for
  maximum freezing injuries

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DSC Thermograms 1xPBS, 1xPBSGlycerol and
1xPBSRaffinose

• Observation
• Eutectic formation disappears when a CPA is
  added.
• Literature in dispute
• Izutsu et al. (1995) reported the similar results
  with the present study using several different
  CPAs.
• Shepard et al. (1976) reported that there was a
  pseudobianry eutectic reaction in a
  water-NaCl-glycerol ternary system.

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DSC Thermograms 5xNaCl-Water and 5xPBS

• 5xNaCl-water
• Freezing process Thermodynamic non-equilibrium
• Thawing process Very close to thermodynamic
  equilibrium
• 5xPBS
• Freezing non-equilibrium
• Thawing equilibrium
• Wider eutectic phase change temperature

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Cryomicroscopy Images Eutectic phase change in
5xPBS
(a) During Freezing (b) During Thawing
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Specific HeatNaCl-water and Phosphate Buffered
Saline (PBS)
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Specific Heat PBSGlycerol and PBSRaffinose
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Effect of Latent Heat Release Pattern Thermal
History of Cryosurgery
Freezing interface Temperature history
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Phase Diagram of a Binary Mixture

• Thermodynamic equilibrium information
• Eutectic formation - Simultaneous solidification
  of water and solutes
• Not only ice nucleation, but eutectic formation
  is also supercooled.