Biothermal Technology Laboratory, Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.
Biothermal Technology Laboratory, Department of Mechanical Engineering, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.
Cryobiology. 2023 Jun;111:9-15. doi: 10.1016/j.cryobiol.2023.03.007. Epub 2023 Mar 21.
This study investigates the feasibility of ice-free isochoric vitrification for cryopreservation applications using mathematical modeling, computation tools, and the underlying principles of thermo-mechanics. This study is triggered by an increasing interest in the possibility of isochoric vitrification, following promising experimental results of isochoric cryopreservation. In general, isochoric cryopreservation is the preservation of biological materials in subzero temperatures in a rigid-sealed container, where some ice crystallization creates favorable pressure elevation due to the anomaly of water expansion upon ice Ih formation. Vitrification on the other hand is the transformation of liquid into an amorphous solid in the absence of any crystals, which is typically achieved by rapid cooling of a highly viscous solution. The current study presents a mathematical model for vitrification under variable pressure conditions, building upon a recently published thermo-mechanics modeling approach for isochoric cryopreservation. Using the physical properties of dimethyl sulfoxide (DMSO) as a representative cryoprotective agent (CPA), this study suggests that vitrification under isochoric conditions is not feasible, essentially since the CPA solution contracts more than the isochoric chamber by an order of magnitude. This differential contraction can lead to absolute zero pressure in the isochoric chamber, counteracting the premise of the isochoric cryopreservation process. It is concluded that the only alternative to prevent ice formation while benefiting from the potential advantages of higher pressures is to create the required pressures by external means, and not merely by passively enclosing the specimen in an isochoric chamber.
本研究通过数学建模、计算工具以及热力学基本原理,探索了无冰等容玻璃化在低温保存应用中的可行性。本研究的起因是等容玻璃化的可能性引起了越来越多的关注,此前等容低温保存的实验结果令人鼓舞。一般来说,等容低温保存是指在刚性密封容器中,将生物材料保存在亚零温度下,在此过程中,由于冰 Ih 形成时水的反常膨胀,一些冰晶的形成会产生有利的压力升高。另一方面,玻璃化是指在没有任何晶体的情况下,将液体转化为非晶固体,这通常通过对高粘性溶液的快速冷却来实现。本研究在最近发表的等容低温保存的热力学建模方法的基础上,提出了一种变压条件下的玻璃化数学模型。以二甲基亚砜(DMSO)作为代表性的抗冻剂(CPA),本研究表明,等容条件下的玻璃化是不可行的,这主要是因为 CPA 溶液的收缩程度比等容室高出一个数量级。这种差异收缩会导致等容室内的绝对零压力,从而与等容低温保存过程的前提相矛盾。结论是,在受益于较高压力的潜在优势的同时,防止冰形成的唯一方法是通过外部手段产生所需的压力,而不仅仅是将标本被动地封闭在等容室内。