State Key Laboratory of Optoelectronic Materials and Technologies, Guangdong Province Key Laboratory of Display Material and Technology, School of Electronics and Information Technology; The First Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou 510006, China.
Pritzker School of Medicine, University of Chicago, Chicago, Illinois 60637, USA.
Nanoscale. 2020 Feb 27;12(8):5103-5113. doi: 10.1039/d0nr00153h.
The detection of circulating tumor cells (CTCs) has achieved promising progress for early diagnosis and disease analysis. Microfluidic chip techniques have recently promoted the technologies of CTC sorting and analysis, yet seldom can the microfluidic chips for CTC enrichment via antibody-free capture provide in situ regulation of both extracellular and intracellular activity, which would be advantageous for cell-based pharmaceutical therapeutics and screening. Herein, we have demonstrated a hybrid TiO2/ZnO branched microtube array (HBMTA)-sandwiched hydrodynamic device that integrates the multiple functions of selective enrichment of adherent tumor cells in an antibody-free manner and in situ delivery to the extracellular and intracellular spaces of the enriched tumor cells. More than 90% cancer cells were enriched on the device due to their preferential adhesion with the nano-branches of HBMTA, while more than 91% blood cells were eliminated from the device by constant hydrodynamic fluid shearing. For in situ regulation, temporally and spatially controlled extracellular delivery to the enriched tumor cells could be precisely achieved through the hollow structures of the HBMTA. In addition, reagents (e.g. propidium iodide) could be delivered into the intracellular spaces of enriched tumor cells by coupling an electric field to nondestructively perforate the cell membrane. Our study not only offers a promising and facile strategy for antibody-free isolation of tumor cells, but also provides unique opportunities to facilitate cancer research, including antitumor drug screening and personalized therapeutics.
循环肿瘤细胞 (CTC) 的检测在早期诊断和疾病分析方面取得了可喜的进展。微流控芯片技术最近推动了 CTC 分选和分析技术的发展，但很少有基于无抗体捕获的微流控芯片能够对细胞外和细胞内活动进行原位调节，这对基于细胞的药物治疗和筛选非常有利。在此，我们展示了一种混合 TiO2/ZnO 分支微管阵列 (HBMTA) 夹合的流体动力学装置，该装置集成了无抗体选择性富集贴壁肿瘤细胞以及原位递送至富集肿瘤细胞的细胞外和细胞内空间的多种功能。由于 HBMTA 的纳米分支对肿瘤细胞具有优先的粘附作用，因此超过 90%的癌细胞被富集在该装置上，而超过 91%的血细胞通过恒流流体剪切从装置中被去除。为了进行原位调节，可以通过 HBMTA 的中空结构精确地实现对富集肿瘤细胞的时空控制的细胞外递药。此外，通过将电场耦合到无损穿孔细胞膜上，可以将试剂（例如碘化丙啶）递送至富集肿瘤细胞的细胞内空间。我们的研究不仅为无抗体分离肿瘤细胞提供了一种有前途且简便的策略，还为癌症研究提供了独特的机会，包括抗肿瘤药物筛选和个性化治疗。
