Deformable L-shaped microwell array for trapping pairs of heterogeneous cells

Deformable L-shaped microwell array for trapping pairs of heterogeneous cells
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DOI:
10.1088/0960-1317/25/3/035005
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发表时间:
2015-03-01
影响因子:
2.3
通讯作者:
Park, Joong Yull
Park, Joong Yull
中科院分区:
工程技术4区
文献类型:
--
作者:
Lee, Gi-Hun;Kim, Sung-Hwan;Park, Joong Yull

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为了研究细胞间的相互作用,人们一直需要开发微系统来捕获微孔阵列中两种不同细胞对。在这里,我们提出了一种l形微孔(L-microwell)阵列,它依赖于聚二甲基硅氧烷(PDMS)底物的弹性来捕获和配对异质细胞。我们设计了一个l-微孔,通过拉伸/释放PDMS底物来捕获每个分支中的单个细胞,并进行了3D时间相关扩散模拟,以可视化细胞分泌的分子如何在l-微孔中扩散并与伴侣细胞通信。计算结果表明,分泌分子在35min后首先与伴侣细胞接触,在4h时(参考分泌分子浓度的10%),分泌分子完全覆盖伴侣细胞。扩散到l -微孔外部的分子被散装溶液显著稀释,从而防止了相邻l -微孔之间不必要的细胞通信。我们在一个2.25 cm(2)的阵列中生产了超过5000个细胞对,大约有30万个l -微孔。所提出的l-微孔阵列提供了一种多功能和方便的细胞配对方法来研究细胞间的相互作用,例如细胞融合、免疫反应和癌症转移。
To study cell-to-cell interactions, there has been a continuous demand on developing microsystems for trapping pairs of two different cells in microwell arrays. Here, we propose an L-shaped microwell (L-microwell) array that relies on the elasticity of a polydimethylsiloxane (PDMS) substrate for trapping and pairing heterogeneous cells. We designed an L-microwell suitable for trapping single cell in each branch via stretching/releasing the PDMS substrate, and also performed 3D time-dependent diffusion simulations to visualize how cell-secreted molecules diffuse in the L-microwell and communicate with the partner cell. The computational results showed that the secreted molecule first contacted the partner cell after 35 min, and the secreted molecule fully covered the partner cell in 4 h (when referenced to 10% of the secreted molecular concentration). The molecules that diffused to the outside of the L-microwell were significantly diluted by the bulk solution, which prevented unwanted cellular communication between neighboring L-microwells. We produced over 5000 cell pairs in one 2.25 cm(2) array with about 30 000 L-microwells. The proposed L-microwell array offers a versatile and convenient cell pairing method to investigate cell-to-cell interactions in, for example, cell fusion, immune reactions, and cancer metastasis.