Theoretical and experimental study of a membrane-based microfluidics for loading and unloading of cryoprotective agents
Theoretical and experimental study of a membrane-based microfluidics for loading and unloading of cryoprotective agents
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膜基微流控冷冻保护剂装载和卸载的理论与实验研究
DOI：
10.1016/j.ijheatmasstransfer.2018.06.137
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发表时间：
2018-12
影响因子：
5.2
通讯作者：
Gao Dayong
中科院分区：
文献类型：
--
作者：
Zhou Xiaoming;Liang Xin M;Wang Ji;Du Pingan;Gao Dayong
细胞常规冷冻保存用于各种应用。成功的冷冻保存需要装载冷冻保护剂（CPAs）以防止细胞在冷冻和解冻期间受到冷冻损伤，以及在使用前卸载CPAs，因为CPAs通常是有毒的。此外，CPA加载/卸载过程通常是费力的并且容易出错。在这项研究中，一个基于膜的微流控装置，以帮助CPA加载和卸载过程。该装置由两个螺旋微流体通道与微滤膜夹层。当细胞悬浮液和置换液在通道中逆流流动时，通过扩散和过滤实现跨膜的CPA交换。细胞悬浮液中的CPA浓度可以以良好控制的渐进方式进行调节。已经开发了一个理论模型，以更好地表征CPA浓度的动态变化和分布，以及细胞体积响应，相对于在CPA加载和卸载步骤期间的设备内的各种传质参数。物理实验已经进行了验证所提出的模型。此外，已建立的模型的指导下，优化的设备的操作条件和不同的设备具有不同的尺寸已被制造，以评估其性能特性相对于不同的吞吐量水平。优化的条件使得能够以180 ml/h的速率加载DMSO（从0%至10%，v/v）并以5 ml/h的速率卸载（从10%至1%，v/v），其中单次通过初始原型。第二个扩大的装置进一步将DMSO卸载速率提高到180 ml/h，洗涤溶液消耗速率为225 ml/h。更高的通量和减少的洗涤溶液需求证明了所提出的方法在效率上的显著进步。最后，该系统易于操作，并且该过程是稳健的，因此为各种尺寸的细胞悬浮液的CPA的装载/卸载提供了可靠的解决方案。
Cells are routinely cryopreserved for various applications. Successful cryopreservation requires the loading of cryoprotective agents (CPAs) to prevent cells from cryoinjury during freezing and thawing, as well as the unloading of CPAs before use since CPAs are often toxic. Moreover, the CPA loading/unloading processes are usually effortful and error-prone. In this study, a membrane-based microfluidic device is introduced to aid the CPA loading and unloading processes. The device consists of two helical microfluidic channels with a sandwiched layer of microfiltration membrane. CPA exchange across the membrane via diffusion and filtration is realized when cell suspension and replacement fluid flow counter-currently in the channels. CPA concentration in the cell suspension can be regulated in a well-controlled, progressive manner. A theoretical model has been developed to better characterize the dynamic change and distribution of the CPA concentration, as well as the cell volume response, with respect to various mass transfer parameters within the device during CPA loading and unloading steps. Physical experiments have been conducted to validate the proposed model. Furthermore, operating conditions of the device have been optimized under the guidance of the established model and different devices with various sizes have been fabricated to evaluate their performance characteristics with respect to different levels of throughput. The optimized condition enables the loading of DMSO (from 0% to 10%, v/v) at a rate of 180 ml/h and unloading (from 10% to 1%, v/v) at 5 ml/h with a single pass through the initial prototype. A second enlarged device further improves the DMSO unloading rate to 180 ml/h with the washing solution consumption rate at 225 ml/h. The higher throughput and reduced washing solution requirement demonstrate the significant advancement in efficiency with the presented approach. Lastly, the system is easy to operate and the process is robust, thus provides a reliable solution for loading/unloading of CPAs for various sized cell suspensions.
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影响因子：
2.9
作者：
C. Valeri;G. Ragno;L. Pivacek;E. O'Neill
通讯作者：
C. Valeri;G. Ragno;L. Pivacek;E. O'Neill
影响因子：
3.3
作者：
A. Mujumdar
通讯作者：
A. Mujumdar
DOI：
10.1016/b978-0-08-098346-2.00003-x
发表时间：
2014
期刊：
--
影响因子：
--
作者：
S. Kandlikar
通讯作者：
S. Kandlikar
影响因子：
3.3
作者：
Arnaud, F;Kapnik, E;Meryman, HT
通讯作者：
Meryman, HT
DOI：
10.1016/j.ijheatmasstransfer.2014.07.026
发表时间：
2014-11
影响因子：
5.2
作者：
T. Scherr;Shelby Pursley;W. Monroe;K. Nandakumar
通讯作者：
T. Scherr;Shelby Pursley;W. Monroe;K. Nandakumar