Sessile Liquid Marbles with Embedded Hydrogels as Bioreactors for Three‐Dimensional Cell Culture
Sessile Liquid Marbles with Embedded Hydrogels as Bioreactors for Three‐Dimensional Cell Culture
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DOI：
10.1002/adbi.202000108
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发表时间：
2021-01
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通讯作者：
R. Vadivelu;N. Kashaninejad;M. Nikmaneshi;R. Khadim;S. S. Salehi-S.;Naveen Chintala Ramulu;Y. Sakai;M. Nishikawa;B. Firoozabadi;N. Nguyen
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作者：
R. Vadivelu;N. Kashaninejad;M. Nikmaneshi;R. Khadim;S. S. Salehi-S.;Naveen Chintala Ramulu;Y. Sakai;M. Nishikawa;B. Firoozabadi;N. Nguyen
基于液体大理石（LM）的数字微流体最近成为液体处理和基于细胞的分析的有前途的平台。然而，蒸发是这类平台的一个关键问题，阻碍了它们在各个领域的广泛应用。本研究旨在开发一种功能稳固的LM系统，用于长期三维细胞培养。此前，该研究小组和其他研究人员证明，漂浮的基于lm的生物反应器可以降低蒸发速率，因此适合生长多细胞球体。然而，浮动LMs不稳定，容易崩溃。本文提出了用琼脂糖凝胶包埋一种蒸发还原型固定式LM。通过一系列综合的数学建模、数值模拟和实验研究（含和不含生物细胞），表明该平台可以作为吸湿系统来控制蒸发，从而延长LMs的寿命。研究还发现，与纯LMs不同，琼脂糖填充的LMs在加湿培养箱中72小时内保持球形。此外，琼脂糖的存在显著有助于减少蒸发，提高收获的多细胞球体的生存能力。这些结果为LMs在生命科学和化学领域的应用开辟了一条新的途径。
Digital microfluidics based on liquid marble (LM) has recently emerged as a promising platform for liquid handling and cell-based assays. However, evaporation is a critical problem in such platforms, hindering their wide-range applications in various fields. This study aims to develop a functional sessile LM system for long-term 3D cell culture. Previously, this study group and others demonstrated that floating LM-based bioreactors could reduce the evaporation rate, and were thus suitable for growing multicellular spheroids. However, floating LMs are not robust and easily collapse. Herein, an evaporation-reducing sessile LM by embedding LM with agarose gel is proposed. Through a series of comprehensive mathematical modeling, numerical simulations, and experimental investigations (both with and without biological cells), it is shown that such a platform acts as a moisture absorption system to control the evaporation and thus extends the life span of LMs. It is also found that unlike pure LMs, the LMs filled with agarose maintain their spherical shapes within 72 h inside a humidified incubator. Moreover, the presence of agarose significantly contributes to minimizing evaporation and improves the viability of the harvested multicellular spheroids. These results can open up a new avenue in using LMs in life sciences and chemistry.