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，即保存处于冻结状态的材料，以及冷冻外科，使用冷冻来破坏组织。这两者都是更大的低温生物学或低温生物学领域的一部分。在这两个应用中，对生物材料热响应(即冷却速度、终止温度、停留时间和解冻速度)的热传递预测对于有效规划方案非常重要，其中生物材料内的热中介事件，如细胞内冰的形成、细胞脱水、共晶形成、(去)玻璃化和/或脂和蛋白质相变化对于决定结果(即生存或死亡)是重要的。不幸的是，对低温状态下的热响应进行准确的热传递预测所需的生物材料热性能数据库相当有限。具体地说，潜热、导热系数和比热性能仅适用于少数生物材料，如果在-40摄氏度以下或在存在化学添加剂的情况下有任何数据，则几乎没有。冰是冻结生物材料的丰富成分，其热扩散率基本上在0到-150摄氏度之间变化一个数量级。初步结果显示，组织中的热性质变化较小，但在冷冻盐溶液中的热性质变化比冰更大。为了更有效地保存或销毁生物材料，添加其他化学品(即冷冻保护剂或冷冻辅助剂)可能会进一步改变生物材料的热性能，其方式尚待确定。这项建议旨在对各种溶液和含有和不含有化学添加剂的天然/人造组织的热物性进行整体和微观尺度的测量，温度低至-150℃。散体测量将使用脉冲衰减式热敏电阻装置进行热导率测量，差示扫描量热仪(DSC)用于比热和潜热测量。此外，将使用一种新的仪器测量定向热导率(各向异性)，该装置允许在定向阶段上观察冰晶在冻结过程中的生长，然后直接根据所显示的样品进行热导率测量。预计，在单个晶体、共晶和玻璃(玻璃化材料)水平上存在的微结构可能具有强烈的各向异性，这可以测量并纳入预测模型。最终，测量的性质将大大有助于低温生物材料热性质数据库的扩展，从而使各种低温生物学应用的预测建模得到改进。

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.