Research Papers

Thermomechanical Stress in Cryopreservation Via Vitrification With Nanoparticle Heating as a Stress-Moderating Effect

[+] Author and Article Information
David P. Eisenberg

Biothermal Technology Laboratory,
Department of Mechanical Engineering,
Carnegie Mellon University,
Pittsburgh, PA 15213

John C. Bischof

Bioheat and Mass Transfer Laboratory,
Department of Mechanical Engineering,
University of Minnesota,
Minneapolis, MN 55455

Yoed Rabin

Biothermal Technology Laboratory,
Department of Mechanical Engineering,
Carnegie Mellon University,
Pittsburgh, PA 15213
e-mail: rabin@cmu.edu

1Corresponding author.

Manuscript received July 12, 2015; final manuscript received November 18, 2015; published online December 8, 2015. Assoc. Editor: Hai-Chao Han.

J Biomech Eng 138(1), 011010 (Dec 08, 2015) (8 pages) Paper No: BIO-15-1343; doi: 10.1115/1.4032053 History: Received July 12, 2015; Revised November 18, 2015

This study focuses on thermomechanical effects in cryopreservation associated with a novel approach of volumetric heating by means on nanoparticles in an alternating electromagnetic field. This approach is studied for the application of cryopreservation by vitrification, where the crystalline phase is completely avoided—the cornerstone of cryoinjury. Vitrification can be achieved by quickly cooling the material to cryogenic storage, where ice cannot form. Vitrification can be maintained at the end of the cryogenic protocol by quickly rewarming the material back to room temperature. The magnitude of the rewarming rates necessary to maintain vitrification is much higher than the magnitude of the cooling rates that are required to achieve it in the first place. The most common approach to achieve the required cooling and rewarming rates is by exposing the specimen's surface to a temperature-controlled environment. Due to the underlying principles of heat transfer, there is a size limit in the case of surface heating beyond which crystallization cannot be prevented at the center of the specimen. Furthermore, due to the underlying principles of solid mechanics, there is a size limit beyond which thermal expansion in the specimen can lead to structural damage and fractures. Volumetric heating during the rewarming phase of the cryogenic protocol can alleviate these size limitations. This study suggests that volumetric heating can reduce thermomechanical stress, when combined with an appropriate design of the thermal protocol. Without such design, this study suggests that the level of stress may still lead to structural damage even when volumetric heating is applied. This study proposes strategies to harness nanoparticles heating in order to reduce thermomechanical stress in cryopreservation by vitrification.

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Sutton, R. L. , 1992, “ Critical Cooling Rates for Aqueous Cryoprotectants in the Presence of Sugars and Polysaccharides,” Cryobiology, 29(5), pp. 585–598. [CrossRef] [PubMed]
Hopkins, J. B. , Badeau, R. , Warkentin, M. , and Thorne, R. E. , 2012, “ Effect of Common Cryoprotectants on Critical Warming Rates and Ice Formation in Aqueous Solutions,” Cryobiology, 65(3), pp. 169–178. [CrossRef] [PubMed]
Rabin, Y. , Taylor, M. J. , Walsh, J. R. , Baicu, S. , and Steif, P. S. , 2005, “ Cryomacroscopy of Vitrification I: A Prototype and Experimental Observations on the Cocktails VS55 and DP6,” Cell Preserv. Technol., 3(3), pp. 169–183. [CrossRef] [PubMed]
Baicu, S. , Taylor, M. J. , Chen, Z. , and Rabin, Y. , 2006, “ Vitrification of Carotid Artery Segments: An Integrated Study of Thermophysical Events and Functional Recovery Toward Scale-Up for Clinical Applications,” Cell Preserv. Technol., 4(4), pp. 236–244. [CrossRef] [PubMed]
Baicu, S. , Taylor, M. J. , Chen, Z. , and Rabin, Y. , 2008, “ Cryopreservation of Carotid Artery Segments Via Vitrification Subject to Marginal Thermal Conditions: Correlation of Freezing Visualization With Functional Recovery,” Cryobiology, 57(1), pp. 1–8. [CrossRef] [PubMed]
Seki, S. , and Mazur, P. , 2009, “ The Dominance of Warming Rate Over Cooling Rate in the Survival of Mouse Oocytes Subjected to a Vitrification Procedure,” Cryobiology, 59(1), pp. 75–82. [CrossRef] [PubMed]
Noday, D. A. , Steif, P. S. , and Rabin, Y. , 2009, “ Viscosity of Cryoprotective Agents Near Glass Transition: A New Device, Technique, and Data on DMSO, DP6, and VS55,” Exp. Mech., 49(5), pp. 663–672. [CrossRef] [PubMed]
Etheridge, M. L. , Xu, Y. , Rott, L. , Choi, J. , Glasmacher, B. , and Bischof, J. , 2014, “ RF Heating of Magnetic Nanoparticles Improves the Thawing of Cryopreserved Biomaterials,” Technology, 2(3), 229–242. [CrossRef]
Ehrlich, L. E. , Feig, J. S. G. , Malen, J. A. , Schiffres, S. N. , and Rabin, Y. , 2013, “ Integration of Transient Hot-Wire Method Into Scanning Cryomacroscopy in the Study of Thermal Conductivity of Dimethyl Sulfoxide,” Cryobiology, 67(3), p. 402.
Fahy, G. M. , Wowk, B. , Pagotan, R. , Chang, A. , Phan, J. , Thomson, B. , and Phan, L. , 2009, “ Physical and Biological Aspects of Renal Vitrification,” Organogenesis, 5(3), pp. 167–175. [CrossRef] [PubMed]
Fahy, G. M. , Wowk, B. , Wu, J. , and Paynter, S. , 2004, “ Improved Vitrification Solutions Based on the Predictability of Vitrification Solution Toxicity,” Cryobiology, 48(1), pp. 22–35. [CrossRef] [PubMed]
Taylor, M. , Song, Y. , and Brockbank, K. , 2004, “ 22 Vitrification in Tissue Preservation: New Developments,” Life in the Frozen State, B. J. Fuller , N. Lane , and E. E. Benson , eds., CRC Press, Boca Raton, FL, pp. 604–641.
Fahy, G. M. , 2004, “ Methods of Using Ice-Controlling Molecules,” U.S. Patent US6773877 B2.
Wowk, B. , and Fahy, G. M. , 2002, “ Inhibition of Bacterial Ice Nucleation by Polyglycerol Polymers,” Cryobiology, 44(1), pp. 14–23. [CrossRef] [PubMed]
Eisenberg, D. P. , Taylor, M. J. , and Rabin, Y. , 2012, “ Thermal Expansion of the Cryoprotectant Cocktail DP6 Combined With Synthetic Ice Modulators in Presence and Absence of Biological Tissues,” Cryobiology, 65(2), pp. 117–125. [CrossRef] [PubMed]
Eisenberg, D. P. , Taylor, M. J. , Jimenez-Rios, J. L. , and Rabin, Y. , 2014, “ Thermal Expansion of Vitrified Blood Vessels Permeated With DP6 and Synthetic Ice Modulators,” Cryobiology, 68(3), pp. 318–326. [CrossRef] [PubMed]
Mehl, P. M. , 1993, “ Nucleation and Crystal Growth in a Vitrification Solution Tested for Organ Cryopreservation by Vitrification,” Cryobiology, 30(5), pp. 509–518. [CrossRef] [PubMed]
Rios, J. L. J. , and Rabin, Y. , 2006, “ Thermal Expansion of Blood Vessels in Low Cryogenic Temperatures, Part II: Vitrification With VS55, DP6, and 7.05 M DMSO,” Cryobiology, 52(2), pp. 284–294. [CrossRef] [PubMed]
Narayanaswamy, O. S. , 1978, “ Stress and Structural Relaxation in Tempering Glass,” J. Am. Ceram. Soc., 61(3–4), pp. 146–152. [CrossRef]
Narayanaswamy, O. S. , 1971, “ A Model of Structural Relaxation in Glass,” J. Am. Ceram. Soc., 54(10), pp. 491–498. [CrossRef]
Plitz, J. , Rabin, Y. , and Walsh, J. , 2004, “ The Effect of Thermal Expansion of Ingredients on the Cocktails VS55 and DP6,” Cell Preserv. Technol., 2(3), pp. 215–226. [CrossRef]
Rabin, Y. , and Plitz, J. , 2005, “ Thermal Expansion of Blood Vessels and Muscle Specimens Permeated With DMSO, DP6, and VS55 at Cryogenic Temperatures,” Ann. Biomed. Eng., 33(9), pp. 1213–1228. [CrossRef] [PubMed]
Jimenez Rios, J. L. , Steif, P. S. , and Rabin, Y. , 2007, “ Stress-Strain Measurements and Viscoelastic Response of Blood Vessels Cryopreserved by Vitrification,” Ann. Biomed. Eng., 35(12), pp. 2077–2086. [CrossRef] [PubMed]
Scherer, G. W. , 1986, Relaxation in Glass and Composites, Wiley, New York.
Eisenberg, D. P. , Steif, P. S. , and Rabin, Y. , 2014, “ On the Effects of Thermal History on the Development and Relaxation of Thermo-Mechanical Stress in Cryopreservation,” Cryogenics, 64, pp. 86–94. [CrossRef] [PubMed]
Steif, P. S. , Palastro, M. C. , and Rabin, Y. , 2008, “ Continuum Mechanics Analysis of Fracture Progression in the Vitrified Cryoprotective Agent DP6,” ASME J. Biomech. Eng., 130(2), p. 021006.
Steif, P. , Palastro, M. , and Rabin, Y. , 2007, “ The Effect of Temperature Gradients on Stress Development During Cryopreservation Via Vitrification,” Cell Preserv. Technol., 5(2), pp. 104–115. [CrossRef] [PubMed]
Rabin, Y. , and Steif, P. S. , 1998, “ Thermal Stresses in a Freezing Sphere and Its Application to Cryobiology,” ASME J. Appl. Mech., 65(2), pp. 328–333. [CrossRef]
Pegg, D. E. , Wusteman, M. C. , and Boylan, S. , 1997, “ Fractures in Cryopreserved Elastic Arteries,” Cryobiology, 34(2), pp. 183–192. [CrossRef] [PubMed]
Hunt, C. J. , Song, Y. C. , Bateson, E. A. , and Pegg, D. E. , 1994, “ Fractures in Cryopreserved Arteries,” Cryobiology, 31(5), pp. 506–515. [CrossRef] [PubMed]
Gordon, C. , 1982, “ Rewarming Mice From Hypothermia by Exposure to 2450-MHz Microwave Radiation,” Cryobiology, 19(4), pp. 428–434. [CrossRef] [PubMed]
Cooper, D. , Ketterer, F. , and Holst, H. , 1981, “ Organ Temperature Measurement in a Microwave Oven by Resonance Frequency Shift,” Cryobiology, 18(4), pp. 378–385. [CrossRef] [PubMed]
Wang, T. , Zhao, G. , Liang, X. M. , Xu, Y. , Li, Y. , Tang, H. , Jiang, R. , and Gao, D. , 2014, “ Numerical Simulation of the Effect of Superparamagnetic Nanoparticles on Microwave Rewarming of Cryopreserved Tissues,” Cryobiology, 68(2), pp. 234–243. [CrossRef] [PubMed]
Burdette, E. , Wiggins, S. , Brown, R. , and Karow, A. K., Jr. , 1980, “ Microwave Thawing of Frozen Kidneys: A Theoretically Based Experimentally-Effective Design,” Cryobiology, 17(4), pp. 393–402. [CrossRef] [PubMed]
Schmehl, M. , Graham, E. , and Kilkowski, S. , 1990, “ Thermographic Studies of Phantom and Canine Kidneys Thawed by Microwave Radiation,” Cryobiology, 27(3), pp. 311–318. [CrossRef] [PubMed]
Phelan, M. , and Douglas, F. , 1982, “ Controlled-Rate Liquid N2—Microwave Biological Freeze—Thaw Device,” Cryobiology, 19(4), pp. 372–391.
Brockbank, K. G. M. , and Taylor, M. J. , 2006, “ Tissue Preservation,” Advances in Biopreservation, J. G. Baust , and J. M. Baust , eds., CRC Press, Boca Raton, FL, pp. 157–196.
Robinson, M. P. , Wusteman, M. C. , Wang, L. , and Pegg, D. E. , 2002, “ Electromagnetic Re-Warming of Cryopreserved Tissues: Effect of Choice of Cryoprotectant and Sample Shape on Uniformity of Heating,” Phys. Med. Biol., 47(13), pp. 2311–2325. [CrossRef] [PubMed]
Evans, S. , 2000, “ Electromagnetic Rewarming: The Effect of CPA Concentration and Radio Source Frequency on Uniformity and Efficiency of Heating,” Cryobiology, 40(2), pp. 126–138. [CrossRef] [PubMed]
Wusteman, M. , Robinson, M. , and Pegg, D. , 2004, “ Vitrification of Large Tissues With Dielectric Warming: Biological Problems and Some Approaches to Their Solution,” Cryobiology, 48(2), pp. 179–189. [CrossRef] [PubMed]
Hergt, R. , Dutz, S. , and Zeisberger, M. , 2010, “ Validity Limits of the Néel Relaxation Model of Magnetic Nanoparticles for Hyperthermia,” Nanotechnology, 21(1), p. 015706. [CrossRef] [PubMed]
Lv, Y. G. , Deng, Z. S. , and Liu, J. , 2005, “ 3-D Numerical Study on the Induced Heating Effects of Embedded Micro/Nanoparticles on Human Body Subject to External Medical Electromagnetic Field,” IEEE Trans. Nanobiosci., 4(4), pp. 284–294. [CrossRef]
Tasci, T. O. , Vargel, I. , Arat, A. , Guzel, E. , Korkusuz, P. , and Atalar, E. , 2009, “ Focused RF Hyperthermia Using Magnetic Fluids,” Med. Phys., 36(5), pp. 1906–1912. [CrossRef] [PubMed]
Hergt, R. , Andra, W. , and D'Ambly, C. , 1998, “ Physical Limits of Hyperthermia Using Magnetite Fine Particles,” IEEE Trans. Magn., 34(5), pp. 3745–3754. [CrossRef]
Steif, P. S. , Palastro, M. , Wan, C.-R. , Baicu, S. , Taylor, M. J. , and Rabin, Y. , 2005, “ Cryomacroscopy of Vitrification, Part II: Experimental Observations and Analysis of Fracture Formation in Vitrified VS55 and DP6,” Cell Preserv. Technol., 3(3), pp. 184–200. [CrossRef] [PubMed]
Jimenez Rios, J. L. , and Rabin, Y. , 2006, “ Thermal Expansion of Blood Vessels in Low Cryogenic Temperatures Part I: A New Experimental Device,” Cryobiology, 52(2), pp. 269–283. [CrossRef] [PubMed]
Rabin, Y. , Steif, P. S. , Hess, K. C. , Jimenez-Rios, J. L. , and Palastro, M. C. , 2006, “ Fracture Formation in Vitrified Thin Films of Cryoprotectants,” Cryobiology, 53(1), pp. 75–95. [CrossRef] [PubMed]
Jimenez Rios, J. L. , and Rabin, Y. , 2007, “ A New Device for Mechanical Testing of Blood Vessels at Cryogenic Temperatures,” Exp. Mech., 47(3), pp. 337–346. [CrossRef]
Feig, J. S. G. , and Rabin, Y. , 2013, “ Integration of Polarized Light Into Scanning Cryomacroscopy,” Cryobiology, 67(3), pp. 399–400. [CrossRef]
Steif, P. S. , Noday, D. A. , and Rabin, Y. , 2009, “ Can Thermal Expansion Differences Between Cryopreserved Tissue and Cryoprotective Agents Alone Cause Cracking?,” Cryo-Lett., 30(6), pp. 414–421.
Jones, S. J. , 1982, “ The Confined Compressive Strength of Polycrystalline Ice,” J. Glaciol., 28(98), pp. 171–177.
Schulson, E. M. , 1990, “ The Brittle Compressive Fracture of Ice,” Acta Metall. Mater., 38(10), pp. 1963–1976. [CrossRef]
Hawkes, I. , and Mellor, M. , 1972, “ Deformation and Fracture of Ice Under Uniaxial Stress,” J. Glaciol., 11(61), pp. 103–131.
Eisenberg, D. P. , and Rabin, Y. , 2015, “ Stress-Strain Measurements in Vitrified Arteries Permeated With Synthetic Ice Modulators,” ASME J. Biomech. Eng., 137(8), p. 081007. [CrossRef]
Aminabhavi, T. M. , and Gopalakrishna, B. , 1995, “ Density, Viscosity, Refractive Index, and Speed of Sound in Aqueous Mixtures of N,N-Dimethylformamide, Dimethylsulfoxide, N,N-Dimethylacetamide, Acetonitrile, Ethylene-Glycol, Diethylene Glycol, 1,4-Dioxane, Tetrahydrofuran, 2-Methodyethanol, and 2-Ethox,” J. Chem. Eng. Data, 40(4), pp. 856–861. [CrossRef]


Grahic Jump Location
Fig. 2

Best-fitted experimental data on VS55 mixed with 5 mg/ml of Fe3O4 nanoparticles: specific heat and specific energy absorption rate due to AC magnetic excitation [8]

Grahic Jump Location
Fig. 3

Thermal history around the sample and at its center for the base-case of surface heating and for the case of added volumetric heating. Also shown are the temperature difference histories across the sample for the above cases, using the reference points illustrated in Fig. 1.

Grahic Jump Location
Fig. 4

Stress history for the case of surface heating driven by the temperature differences displayed in Fig. 3 (points O and W are illustrated in Fig. 1, while labels mark the axial stress only)

Grahic Jump Location
Fig. 5

Stress history for the case of added volumetric heating driven by the temperature differences displayed in Fig. 3 (points O and W are illustrated in Fig. 1, while labels mark the axial stress only)

Grahic Jump Location
Fig. 6

Axial stress history at the wall for the case of volumetric heating subject to various cooling rates at the cooling phase of the protocol (segment B–F), with reference to the based case: 20% slower (9.4 °C/min), nominal rate (11.8 °C/min), 10% faster (13.0 °C/min), and 20% faster (14.2 °C/min); labels mark the base case only

Grahic Jump Location
Fig. 7

Axial stress history at the wall for the case of volumetric heating subject to variable heat transfer rates at the surface, where the inset displays the entire stress history for the base case, while the only section affected by heating is shown in greater detail (segment F–H)

Grahic Jump Location
Fig. 1

Schematic illustration of the thermal problem, where reference points O and W are used for discussion purposes



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