NanoVelcro rare-cell assays for detection and characterization of circulating tumor cells.

NanoVelcro rare-cell assays for detection and characterization of circulating tumor cells.
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DOI:
10.1016/j.addr.2018.03.006
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发表时间:
2018-02-01
影响因子:
16.1
通讯作者:
Tseng HR
Tseng HR
中科院分区:
医学1区
文献类型:
--
作者:
Jan YJ;Chen JF;Zhu Y;Lu YT;Chen SH;Chung H;Smalley M;Huang YW;Dong J;Chen LC;Yu HH;Tomlinson JS;Hou S;Agopian VG;Posadas EM;Tseng HR

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循环肿瘤细胞(CTC)是从原发性肿瘤或转移部位切碎的癌细胞,并作为转移的潜在细胞来源在血液中循环。通过检测和分析CTC,我们将能够无创地监测个体癌症患者的疾病进展,并获得评估疾病状态的有洞察力的信息,从而实现“肿瘤液体活检”的概念。然而,由于大量血液细胞中CTC的丰度极低,因此在技术上鉴定患者血液样品中的CTC具有挑战性。为了应对这一挑战,我们在加州大学洛杉矶分校的研究团队开创了“NanoVelcro”细胞亲和基底的独特概念,其中CTC捕获剂涂覆的纳米结构基底被用于以显著的效率捕获CTC。在过去的十年中,已经开发了四代NanoVelcro CTC检测试剂盒,用于各种临床用途。第一代NanoVelcro芯片由硅纳米线衬底(SiNS)和覆盖的微流体混沌混合器组成,用于CTC计数。第二代NanoVelcro芯片(即,NanoVelcro-LMD)基于聚合物纳米基底,被开发用于结合使用激光显微切割(LMD)技术的单CTC分离。通过将热敏聚合物刷接枝到SiNS上,第三代热敏NanoVelcro芯片已经证明了分别在37和4 °C下捕获和释放CTC,从而允许快速CTC纯化,同时保持细胞活力和分子完整性。第四代NanoVelcro芯片(Sweet chip)在芯片表面上用硼酸接枝的基于导电聚合物的纳米材料制造,能够纯化具有保存良好的RNA转录物的CTC,其可用于几种癌症特异性RNA生物标志物的下游分析。在这篇综述文章中,我们将总结四代NanoVelcro CTC Assays的发展,以及每一代设备的临床应用。
Circulating tumor cells (CTCs) are cancer cells shredded from either a primary tumor or a metastatic site and circulate in the blood as the potential cellular origin of metastasis. By detecting and analyzing CTCs, we will be able to noninvasively monitor disease progression in individual cancer patients and obtain insightful information for assessing disease status, thus realizing the concept of “tumor liquid biopsy”. However, it is technically challenging to identify CTCs in patient blood samples because of the extremely low abundance of CTCs among a large number of hematologic cells. In order to address this challenge, our research team at UCLA pioneered a unique concept of “NanoVelcro” cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with remarkable efficiency. Four generations of NanoVelcro CTC assays have been developed over the past decade for a variety of clinical utilities. The 1st-gen NanoVelcro chips, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, were created for CTC enumeration. The 2nd-gen NanoVelcro chips (i.e., NanoVelcro-LMD), based on polymer nanosubstrates, were developed for single-CTC isolation in conjunction with the use of the laser microdissection (LMD) technique. By grafting thermoresponsive polymer brushes onto SiNS, the 3rd-gen Thermoresponsive NanoVelcro chips have demonstrated the capture and release of CTCs at 37 and 4 °C respectively, thereby allowing for rapid CTC purification while maintaining cell viability and molecular integrity. Fabricated with boronic acid-grafted conducting polymer-based nanomaterial on chip surface, the 4th-gen NanoVelcro Chips (Sweet chip) were able to purify CTCs with well-preserved RNA transcripts, which could be used for downstream analysis of several cancer specific RNA biomarkers. In this review article, we will summarize the development of the four generations of NanoVelcro CTC Assays, and the clinical applications of each generation of devices.
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发表时间: 2004-08-19
影响因子: 158.5
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