Thermal Characterization and Modeling of Intracellular Solution during Cooling

人工组织、脐带血疗法、细胞移植程序的出现以及储存生殖（卵/精子）细胞的愿望推动了建立可靠储存生物材料的方法的需求。 超低温保存是一种有效的方法来储存生物材料，而不会在很长一段时间内发生功能性降解。 低温保存的主要挑战是降低生物材料的温度，而不会通过脱水或过度冰晶形成破坏细胞。 目前，大量利用实验来建立最佳的冷冻保存冷却程序。 实验开发冷却程序所需的成本，时间和缺乏某些生物材料（如人类卵细胞）正在推动数学模型的发展，以预测冷却时的热工水力行为。 该项目的成果是一种工具，将提供可用于这种模型的单电池的热性能信息。关于该项目的智力价值，将开发的微差示扫描量热仪（microDSC）将比现有的差示扫描量热仪灵敏至少100倍。 提高的灵敏度将允许直接测量细胞内相变温度。 假设使用实际的细胞内相变温度，而不是假设细胞内液具有与细胞外溶液相同的相变温度，将提高模型的预测能力。将要开发的功能齐全的microDSC和低温保存模型的改进，将使低温生物学家不必进行大量的实验，以获得最佳的低温保存效果。冷却程序。 由于数学模型将能够预测成功的冷冻保存程序，因此可以有效冷冻保存的细胞和组织类型的数量将加快。 除了提高冷冻保存模型的预测能力外，预计microDSC将通过修改控制算法来研究细胞级样品内的冰晶形成。 该工具将利用热电元件，可以根据所施加电流的大小和极性为样本提供规定量的加热或冷却。 其他需要精确温度控制的生物相变应用的研究，例如蛋白质的构型变化，也可以使用该工具。 对细胞内结构的深入了解也将是可能的。 最后，预计了解单个细胞的相变现象将允许开发更准确的细胞团模型，如器官。 这些改进的器官模型将提高我们目前延长移植器官存活期的能力。

CBET-0828271SolbrekkenThe advent of artificial tissues, cord blood therapies, cell transplantation procedures, and the desire to bank germ (egg/sperm) cells have driven the need to establish a means to reliably store biological materials. Cryopreservation is an effective means to store biological materials without functional degradation over a prolonged period of time. The primary cryopreservation challenge is to lower the temperature of biological materials without destroying the cells through dehydration or excessive ice crystal formation. Currently, experiments are heavily utilized in order to establish optimum cryopreservation cooling procedures. The cost, time, and lack of certain biological materials (such as human egg cells) required to experimentally develop cooling procedures are driving the development of mathematical models to predict thermal-hydraulic behavior upon cooling. The outcome of this project is a tool that will provide thermal property information of single cells that can be used in such models.With respect to the intellectual merit of this project, the micro-differential scanning calorimeter (microDSC) to be developed will be at least 100 times more sensitive than currently available differential scanning calorimeters. The heightened sensitivity will allow the intracellular phase change temperature to be measured directly. It is hypothesized that using the actual intracellular phase change temperature, as opposed to assuming the intracellular fluid to have the same phase change temperature as the extracellular solution, will improve the predictive capabilities of the models.As for the broader impacts, the fully functional microDSC and cryopreservation model improvements that will be developed will relieve cryobiologists of the large number of experiments needed to obtain an optimum cooling procedure. The number of cell and tissue types that can be effectively cryopreserved will be accelerated as the mathematical models will be capable of predicting successful cryopreservation procedures. In addition to improving the predictive capability of the cryopreservation models, it is expected that the microDSC will allow studies of ice crystal formation within cell scale samples by modifying the control algorithm. The tool will utilize thermoelectric elements that can provide a prescribed amount heating or cooling to the sample based on the magnitude and polarity of the applied electric current. Investigations of other biological phase changes applications where precise temperature control is required, such as configuration changes in proteins, could be possible with this tool as well. Insights into the intracellular structure will also be possible. Finally, it is expected that understanding the phase change phenomena of individual cells will allow more accurate models of cell masses, such as organs, to be developed. Those improved organ models will improve our current ability to prolong the viable life of organs for transplant.