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用于细胞分离和细胞检测的微孔阵列微制造

Microfabrication of Micropore Array for Cell Separation and Cell Assay.

作者信息

Liu Yaoping, Xu Han, Zhang Lingqian, Wang Wei

机构信息

Institute of Microelectronics, Peking University, Beijing 100871, China.

R&D Center of Healthcare Electronics, Institute of Microelectronics, Chinese Academy of Sciences, Beijing 100029, China.

出版信息

Micromachines (Basel). 2018 Nov 24;9(12):620. doi: 10.3390/mi9120620.

Abstract

Micropore arrays have attracted a substantial amount of attention due to their strong capability to separate specific cell types, such as rare tumor cells, from a heterogeneous sample and to perform cell assays on a single cell level. Micropore array filtration has been widely used in rare cell type separation because of its potential for a high sample throughput, which is a key parameter for practical clinical applications. However, most of the present micropore arrays suffer from a low throughput, resulting from a low porosity. Therefore, a robust microfabrication process for high-porosity micropore arrays is urgently demanded. This study investigated four microfabrication processes for micropore array preparation in parallel. The results revealed that the Parylene-C molding technique with a silicon micropillar array as the template is the optimized strategy for the robust preparation of a large-area and high-porosity micropore array, along with a high size controllability. The Parylene-C molding technique is compatible with the traditional micromechanical system (MEMS) process and ready for scale-up manufacture. The prepared Parylene-C micropore array is promising for various applications, such as rare tumor cell separation and cell assays in liquid biopsy for cancer precision medicine.

摘要

微孔阵列因其能够从异质样本中高效分离特定细胞类型(如稀有肿瘤细胞)并在单细胞水平上进行细胞分析的强大能力而备受关注。微孔阵列过滤因其具有高通量潜力,已广泛应用于稀有细胞类型分离,而高通量是实际临床应用的关键参数。然而,目前大多数微孔阵列由于孔隙率低而导致通量较低。因此,迫切需要一种用于制备高孔隙率微孔阵列的稳健微制造工艺。本研究同时考察了四种用于制备微孔阵列的微制造工艺。结果表明,以硅微柱阵列作为模板的聚对二甲苯-C模塑技术是稳健制备大面积、高孔隙率微孔阵列以及具有高尺寸可控性的优化策略。聚对二甲苯-C模塑技术与传统微机电系统(MEMS)工艺兼容,可进行规模化制造。所制备的聚对二甲苯-C微孔阵列在多种应用中具有广阔前景,如在癌症精准医学的液体活检中用于稀有肿瘤细胞分离和细胞分析。

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