Photo- and electropatterning of hydrogel-encapsulated living cell arrays
Photo- and electropatterning of hydrogel-encapsulated living cell arrays
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DOI：
10.1039/b406953f
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发表时间：
2005-01-01
期刊：
影响因子：
6.1
通讯作者：
Bhatia, SN
中科院分区：
文献类型：
--
作者：
Albrecht, DR;Tsang, VL;Bhatia, SN
活细胞有潜力作为传感器，自然地整合对刺激的反应，产生对细胞命运的预测(例如，分化、迁移、增殖、凋亡)。活细胞的小型化阵列进一步提供了并行询问多个细胞的能力，从而实现了高通量和/或组合分析。然而，活细胞和合成芯片平台之间的界面是一个关键的界面，其中必须保存细胞表型才能产生有用的信号。虽然一些细胞类型在平面(2-D)上保留了组织特有的特征，但越来越明显的是，其他类型的细胞需要3-D物理环境。在这篇文章中，我们提出了两种独立的方法来创建活细胞阵列，这些活细胞阵列被封装在基于聚乙二醇水凝胶中，以创建局部的三维微环境。首先，“光调制”选择性地将水凝胶微结构交联，水凝胶微结构中含有特征尺寸接近100微米的活细胞。其次，“电图案化”利用介电泳力在交联剂之前将细胞定位在预聚体溶液中，形成微米分辨率的细胞图案。我们进一步结合这些方法来获得从微米到厘米的长度尺度上的细胞定位的分级控制。这种水平的微环境控制应该能够制造下一代细胞微阵列，在这种微阵列中，强大的3-D细胞培养被呈现适当的物理和化学线索，从而报告类似体内行为的细胞反应。
Living cells have the potential to serve as sensors, naturally integrating the response to stimuli to generate predictions about cell fate ( e. g., differentiation, migration, proliferation, apoptosis). Miniaturized arrays of living cells further offer the capability to interrogate many cells in parallel and thereby enable high-throughput and/or combinatorial assays. However, the interface between living cells and synthetic chip platforms is a critical one wherein the cellular phenotype must be preserved to generate useful signals. While some cell types retain tissue-specific features on a flat (2-D) surface, it has become increasingly apparent that a 3-D physical environment will be required for others. In this paper, we present two independent methods for creating living cell arrays that are encapsulated within a poly(ethyleneglycol)-based hydrogel to create a local 3-D microenvironment. First, 'photopatterning' selectively crosslinks hydrogel microstructures containing living cells with similar to100 mum feature size. Second, 'electropatterning' utilizes dielectrophoretic forces to position cells within a prepolymer solution prior to crosslinking, forming cell patterns with micron resolution. We further combine these methods to obtain hierarchical control of cell positioning over length scales ranging from microns to centimeters. This level of microenvironmental control should enable the fabrication of next-generation cellular microarrays in which robust 3-D cultures of cells are presented with appropriate physical and chemical cues and, consequently, report on cellular responses that resemble in vivo behavior.