William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.
Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Methods Mol Biol. 2023;2679:67-81. doi: 10.1007/978-1-0716-3271-0_5.
Selectively capturing and releasing viable circulating tumor cells (CTCs) from the peripheral blood of cancer patients is advantageous for investigating the molecular hallmarks of metastasis and developing personalized therapeutics. CTC-based liquid biopsies are flourishing in the clinical setting, offering opportunities to track the real-time responses of patients during clinical trials and lending accessibility to cancers that are traditionally difficult to diagnose. However, CTCs are rare compared to the breadth of cells that reside in the circulatory network, which has encouraged the engineering of novel microfluidic devices. Current microfluidic technologies either extensively enrich CTCs but compromise cellular viability or sort viable CTCs at low efficiencies. Herein we present a procedure to fabricate and operate a microfluidic device capable of capturing CTCs at high efficiencies while ensuring high viability. The microvortex-inducing microfluidic device functionalized with nanointerfaces positively enriches CTCs via cancer-specific immunoaffinity, while a thermally responsive surface chemistry releases the captured cells by raising the temperature to 37 °C.
从癌症患者的外周血液中选择性地捕获和释放有活力的循环肿瘤细胞(CTCs),有利于研究转移的分子特征并开发个性化治疗方法。基于 CTC 的液体活检在临床环境中蓬勃发展,为在临床试验期间跟踪患者的实时反应提供了机会,并为传统上难以诊断的癌症提供了可及性。然而,与循环网络中存在的细胞数量相比,CTCs 非常罕见,这鼓励了新型微流控设备的工程设计。目前的微流控技术要么广泛富集 CTCs,但会损害细胞活力,要么以低效率对有活力的 CTCs进行分类。在这里,我们介绍了一种制造和操作微流控设备的方法,该设备能够以高效率捕获 CTCs,同时确保高活力。功能化纳米界面的微涡旋诱导微流控设备通过癌症特异性免疫亲和性积极富集 CTCs,而通过将温度升高到 37°C 的热响应表面化学释放捕获的细胞。