Quantification of the Biotransport Phenomena in Low-Cryoprotectant (CPA) Vitrification of Living Cells

1033426由于结冰或使用高浓度的冷冻保护剂(CPA)的有害影响，目前的细胞冷冻保存方法往往会产生低产量的活细胞。这项研究寻求使用低浓度、无毒的CPA(Low-CPA)实现细胞的无冰冷冻保存(玻璃化)。到目前为止，对活细胞中水在低CPA玻璃化过程中的热驱动、非平衡相变为晶体或玻璃固体及其与细胞存活的相关性的定量理解尚未实现。因此，本项目的目标是通过模型开发和实验验证来量化相关的基本现象。智力优势：将开发一个耦合的热和相变模型，该模型将有助于定量理解低CPA玻璃化过程中的相关生物运输过程。将确定用于冷冻保存各种活细胞的最佳低CPA玻璃化冷冻方案。更广泛的影响：拟议的研究将有助于推进新兴的基于细胞的医学，其最终的成功取决于保存活细胞以便分发给最终用户的能力。此外，拟议的研究将通过以下方式纳入教育：(A)课程开发，(B)对研究生、本科生和高中生的培训，以及(C)通过专门网页传播研究结果。

1033426HeContemporary methods for cell cryopreservation often produce a low yield of viable cells due to the harmful effects of ice formation or use of a high concentration of cryoprotectant (CPA). This research seeks to achieve ice-free cryopreservation (vitrification) of cells using a low, nontoxic concentration of CPA (low-CPA). A quantitative understanding of the thermally driven, non-equilibrium phase transition of water in living cells into either a crystalline or a glassy solid, and its correlation with cell survival during low-CPA vitrification has not been achieved to date. Therefore, the objective of this project is to quantify the relevant fundamental phenomena by model development coupled with experimental verification.Intellectual Merit: A coupled thermal and phase transition model will be developed which will facilitate quantitative understanding of the pertinent biotransport processes during low-CPA vitrification. Optimal low-CPA vitrification protocols for cryopreserving various living cells will be determined. Broader Impacts: The proposed research will assist the advancement of emerging cell-based medicine of which the eventual success relies upon the capability to preserve living cells for distribution to end users. Moreover, the proposed research will be integrated into education through (a) curriculum development, (b) training of graduate, undergraduate, and high school students, and (c) dissemination of the research findings including by a specialized web page.