Micro and Macroscale Measurement of Thermal Properties for Cryobiological Applications

冷冻的两个重要的生物医学应用是冷冻保存，即在冷冻状态下保存材料，以及冷冻手术，即使用冷冻来破坏组织。 这两者都是低温生物学或低温生物学更大领域的一部分。 在这两种应用中，生物材料热响应的传热预测（即，冷却速率、终温、停留时间和解冻速率）对于有效规划方案是重要的，其中生物材料内的热介导事件例如细胞内冰形成、细胞脱水、共晶形成，（去）玻璃化，和/或脂质和蛋白质相的变化对于确定结果（即存活或死亡）是重要的。不幸的是，在低温状态下进行准确的热传递预测所需的生物材料热特性数据库是相当有限的。 具体而言，潜热，导热系数和比热性能仅适用于少数生物材料，并且在-40 ℃以下或存在化学添加剂的情况下几乎没有任何数据。 冰是冷冻生物材料的丰富组分，其热扩散率在0和-150 ℃之间基本上变化一个数量级。 初步结果显示，组织中的热性质变化更温和，但冷冻盐溶液中的热性质变化甚至比冰更大。 为了更有效地保存或破坏生物材料而添加其他化学品（即冷冻保护剂或冷冻佐剂）可能会进一步改变热特性，其方式仍有待确定。该提案旨在对各种溶液和天然/人造组织的热性能进行批量和微尺度测量，其中有和没有化学添加剂，温度低至-150 ℃。 将使用用于热导率测量的脉冲衰减热敏电阻装置和用于比热和潜热测量的差示扫描量热法（DSC）进行本体测量。（各向异性），其取决于微尺度冰晶结构和取向，将使用一种新的装置进行测量，该装置允许在定向阶段冷冻期间观察冰晶生长，然后直接在样品可视化。 预计在单个晶体、共晶体和玻璃（玻璃化材料）水平上存在的微结构可能具有强的各向异性性质，其可以被测量并并入预测模型中。 最终，所测量的性能将大大有助于低温生物材料热性能数据库的扩展，从而允许各种低温生物学应用的改进的预测建模。

Two important biomedical applications of freezing are cryopreservation, the preservation of material in the frozen state, and cryosurgery, the use of freezing to destroy tissue. These both are part of the larger field of cryobiology or low temperature biology. In both of these applications heat transfer prediction of biomaterial thermal response (i.e. cooling rate, end-temperature, dwell time and thawing rate) is important for the effective planning of protocols where thermally mediated events within the biomaterial such as intracellular ice formation, cellular dehydration, eutectic formation, (de)vitrification, and/or lipid and protein phase changes are important to the determination of outcome (i.e. survival or death). Unfortunately the database of biomaterial thermal properties necessary to make accurate heat transfer prediction of thermal response in the cryogenic regime is quite limited. Specifically, latent heat, thermal conductivity and specific heat properties are available only for a few biomaterials and little if any data is available below -40 C or in the presence of chemical additives. The thermal diffusivity of ice, an abundant component of frozen biomaterials, changes by essentially an order of magnitude between 0 and -150 C. Preliminary results show more modest thermal property changes in tissues, but even greater thermal property changes in frozen salt solutions than ice. The addition of other chemicals (i.e. cryoprotective agents or cryoadjuvants) in order to more effectively preserve or destroy the biomaterial may further alter the thermal properties in a manner which remains to be determined. This proposal aims to make both bulk and microscale measurements of thermal properties for a variety of solutions and native/artificial tissues with and without chemical additives down to a temperature of -150 C. Bulk measurements will be carried out with a pulse-decay thermistor apparatus for thermal conductivity measurement and a Differential Scanning Calorimetry (DSC) for specific heat and latent heat measurements.In addition, directional thermal conductivity (anisotropy), which depends on microscale ice crystal structure and orientation, will be measured with a new apparatus which allows visualization of ice crystal growth during freezing on a directional stage followed by thermal conductivity measurements directly on the sample visualized. It is anticipated that the presence of microstructure at the level of the individual crystals, eutectics and glass (vitrified material) may have a strong anisotropic nature which can be measured and incorporated into predictive models. Ultimately, the properties measured will contribute significantly to the expansion of a cryogenic biomaterial thermal property database thereby allowing improved predictive modeling for a variety of cryobiological applications.