Micromachine-enabled capture and isolation of cancer cells in complex media.
Micromachine-enabled capture and isolation of cancer cells in complex media.
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DOI：
10.1002/anie.201100115
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发表时间：
2011-04-26
影响因子：
16.6
通讯作者：
Wang, Joseph
中科院分区：
文献类型：
--
作者：
Balasubramanian, Shankar;Kagan, Daniel;Hu, Che-Ming Jack;Campuzano, Susana;Lobo-Castanon, M. Jesus;Lim, Nicole;Kang, Dae Y.;Zimmerman, Maria;Zhang, Liangfang;Wang, Joseph
循环肿瘤细胞（CTC）是引起癌症转移的主要实体。CTC的检测为各种类型癌症的临床诊断和预后提供了指标。已经描述了几种主要基于使样品流过抗体包被的磁珠[1]或微芯片[2，3]表面的方法用于分离和计数CTC。然而，这些方法需要大量的样品制备和/或复杂的表面微结构来检测血液中极低丰度的CTC。[3，4]在这项研究中，我们描述了一种基于免疫微机器的体外分离癌细胞的方法，该方法有望在不进行样品预处理的情况下直接检测CTC。人造纳米机器领域的最新进展，[5]特别是人造纳米电机在功率，效率，运动控制和多功能性方面的重大进展，[6]已经打开了新的重要生物医学应用的大门。从药物输送[7]到生物传感。[8]自动移动的合成纳米马达最近已被用于拾取和运输各种有效载荷，主要是通过磁或静电相互作用。[9]将化学动力纳米马达的范围扩展到生理条件是一个关键挑战，因为这种纳米马达通常与生物流体的高离子强度环境不相容。由积聚的气泡的反冲力推动的催化卷起的微管火箭[6a，9d，e，10]对于分离和运输癌细胞用于下游分析特别有吸引力，因为它们具有携带大型哺乳动物细胞所需的牵引力。在这里，我们证明，这些微火箭克服了以前的限制，在生物液体中的运动，并很容易与癌细胞上表达的抗原表面蛋白，如抗癌胚抗原（抗CEA）单克隆抗体（mAb）的抗体特异性功能。[11]CEA被用作靶向抗原，因为它是癌细胞中最常见的抗原之一，在大约95%的结肠直肠癌、胃癌和胰腺癌中过表达。[12]图1概念性地示出了基于微火箭的癌细胞的拾取和运输。使用标准EDC/NHS化学，通过二元自组装单层（SAM）的羧基封端基团实现抗CEA mAb与微火箭外金表面的偶联（详情参见图1和实验部分中的插图）。
Circulating tumor cells (CTCs) are the primary entities responsible for spawning cancer metastasis. Detection of CTCs provides an indicator for the clinical diagnosis and prognosis of various types of cancers. Several approaches, based primarily on flowing the sample through antibody-coated magnetic-beads [1] or microchip [2, 3] surfaces have been described for isolating and counting CTCs. However, these approaches require extensive sample preparation and/or complex surface microstructures to detect the extremely low abundance of CTCs in blood.[3, 4] In this study we describe a immunomicromachine-based approach for an in-vitro isolation of cancer cells that holds promise for direct CTC detection without sample pre-processing.Recent progress in the field of man-made nanomachines,[5] particularly major advances in the power, efficiency, motion control and versatility of artificial nanomotors,[6] have opened the door to new and important biomedical applications, ranging from drug delivery [7] to biosensing.[8] Autonomously moving synthetic nanomotors have recently been employed for the pickup and transport of diverse payloads, mostly via magnetic or electrostatic interactions.[9] Extending the scope of chemically-powered nanomotors to physiological conditions represents a key challenge since such nanomotors are commonly incompatible with the high ionic strength environment of biological fluids. Catalytic rolled-up microtube rockets, propelled by the recoiling force of accumulated gas bubbles,[6a, 9d, e, 10] are particularly attractive for isolating and transporting cancer cells for downstream analysis as they possess the necessary towing force to carry large mammalian cells. Here we demonstrate that these microrockets overcome previous constraints to locomotion in biological fluids and are readily functionalized with an antibody specific for antigenic surface proteins expressed on cancer cells, such as anti-carcinoembryonic antigen (anti-CEA) monoclonal antibody (mAb).[11] CEA is used as a targeting antigen because it is one of the most common antigens among cancer cells, being over-expressed in approximately 95% of colorectal, gastric and pancreatic cancers.[12] Figure 1 conceptually illustrates the microrockets based pick-up and transport of cancer cells. The conjugation of the anti-CEA mAb to the outer gold surface of the microrockets is accomplished through carboxylterminated groups from a binary self-assembled monolayer (SAM) using standard EDC/NHS chemistry (see inset in Figure 1 and Experimental Section for details).
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影响因子：
19
作者：
Solovev, Alexander A.;Sanchez, Samuel;Schmidt, Oliver G.
通讯作者：
Schmidt, Oliver G.
影响因子：
10.8
作者：
Zhang, Li;Abbott, Jake J.;Nelson, Bradley J.
通讯作者：
Nelson, Bradley J.
影响因子：
3
作者：
Mallouk, Thomas E.;Sen, Ayusman
通讯作者：
Sen, Ayusman
影响因子：
17.1
作者：
Manesh, Kalayil Manian;Cardona, Maria;Wang, Joseph
通讯作者：
Wang, Joseph
影响因子：
13.3
作者：
Solovev, Alexander A.;Mei, Yongfeng;Schmidt, Oliver G.
通讯作者：
Schmidt, Oliver G.