Department of Chemical Engineering, University of Wyoming, Laramie, WY 82071, United States; Department of Biomolecular and Chemical Engineering, University of Delaware, Newark, DE 19716, United States.
Department of Chemical and Biological Engineering, University of Colorado Boulder,Boulder, CO 80309, United States; Department of Mechanical and Process Engineering, ETH Zürich, Zürich, 8092, Switzerland.
Colloids Surf B Biointerfaces. 2019 Feb 1;174:483-492. doi: 10.1016/j.colsurfb.2018.11.049. Epub 2018 Nov 20.
Circulating tumor cells (CTCs) play a central role in cancer metastasis and represent a rich source of data for cancer prognostics and therapeutic guidance. Reliable CTC recovery from whole blood therefore promises a less invasive and more sensitive approach to cancer diagnosis and progression tracking. CTCs, however, are exceedingly rare in whole blood, making their quantitative recovery challenging. Several techniques capable of isolating these rare cells have been introduced and validated, yet most suffer from low CTC purity or viability, both of which are essential to develop a clinically viable CTC isolation platform. To address these limitations, we introduce a patterned, immunofunctional, photodegradable poly(ethylene glycol) (PEG) hydrogel capture surface for the isolation and selective release of rare cell populations. Flat and herringbone capture surfaces were successfully patterned via PDMS micromolding and photopolymerization of photolabile PEG hydrogels. Patterned herringbone surfaces, designed to convectively transport cells to the capture surface, exhibited improved capture density relative to flat surfaces for target cell capture from buffer, buffy coat, and whole blood. Uniquely, captured cells were released for collection by degrading the hydrogel capture surface with either bulk or targeted irradiation with cytocompatible doses of long wavelength UV light. Recovered cells remained viable following capture and release and exhibited similar growth rates as untreated control cells. The implementation of molded photodegradable PEG hydrogels as a CTC capture surface provides a micropatternable, cytocompatible platform that imparts the unique ability to recover pure, viable CTC samples by selectively releasing target cells.
循环肿瘤细胞 (CTCs) 在癌症转移中起着核心作用，是癌症预后和治疗指导的丰富数据来源。因此，从全血中可靠地回收 CTC 有望提供一种侵入性更小、更敏感的癌症诊断和进展跟踪方法。然而，CTCs 在全血中极为罕见，使得它们的定量回收具有挑战性。已经引入并验证了几种能够分离这些稀有细胞的技术，但大多数技术的 CTC 纯度或活力都较低，这两者对于开发临床可行的 CTC 分离平台都是至关重要的。为了解决这些限制，我们引入了一种图案化的、免疫功能化的、光降解的聚乙二醇 (PEG) 水凝胶捕获表面，用于稀有细胞群体的分离和选择性释放。通过 PDMS 微成型和光不稳定 PEG 水凝胶的光聚合，可以成功地对平纹和人字形捕获表面进行图案化。设计用于将细胞对流输送到捕获表面的人字形捕获表面相对于平面表面在从缓冲液、白细胞层和全血中捕获靶细胞方面表现出更高的捕获密度。独特的是，通过用大体积或靶向辐照用细胞相容性的长波长紫外光降解水凝胶捕获表面，可以释放捕获的细胞以进行收集。捕获和释放后，回收的细胞仍然保持活力，并且表现出与未经处理的对照细胞相似的生长速度。作为 CTC 捕获表面的模制光降解 PEG 水凝胶的实施提供了一种微图案化的、细胞相容性的平台，赋予了通过选择性释放靶细胞来回收纯的、存活的 CTC 样品的独特能力。
