乳腺癌循环肿瘤细胞微流控芯片检测研究进展
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1.中国人民解放军空军军医大学第一附属医院 甲乳血管外科,陕西 西安710032;2.西安电子科技大学 生命科学技术学院,陕西 西安710126

作者简介:

尉卓凡,中国人民解放军空军军医大学第一附属医院硕士研究生,主要从事乳腺癌早期诊断与治疗方面的研究。

基金项目:

陕西省自然科学基础研究计划重点基金资助项目(2021JZ-26)。


Research progress of microfluidic chip detection of circulating tumor cells in breast cancer
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1.Department of Thyroid, Breast and Vascular Surgery, the First Affiliated Hospital of Air Force Military Medical University, Xi'an 710032, China;2.School of Life Science and Technology, Library, Xidian University, Xi'an 710126, China

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    摘要:

    乳腺癌是女性最常见的恶性肿瘤。不可预测的转移性复发是乳腺癌患者治疗失败、复发乃至死亡的主要原因。循环肿瘤细胞(CTC)被定义为从原发肿瘤处脱落并进入循环或淋巴系统的肿瘤细胞。研究证实,CTC的检测可以为乳腺癌的诊断、治疗策略的制定和预后评估提供重要的临床信息。作为液体活检的重要检测对象之一,CTC能够简单地通过抽取患者的血液来收集。然而,大多数CTC在循环中死亡,只有极少数存活并侵犯远处器官。数量上的稀缺、CTC的异质性以及血液中复杂成分的干扰使得CTC的准确检测成为一个巨大的挑战。针对CTC的生物和物理特性开发的各种检测方法往往需要在检测前对CTC进行分离和富集,但吸附、洗脱和转移等预处理过程不可避免地会造成CTC的损失,而耗时、操作复杂、设备昂贵等问题也限制了CTC的临床应用,因此迫切需要开发新的检测技术。以微加工结构为特征的微流控技术近年来受到了广泛关注与研究,微流控技术可以精确控制微米级的流体和细胞,因而成为一种特别适合检测稀有CTC的方法。微流控芯片具有成本低、操作简单、低耗材、高通量、实时检测等优势,其小型化的特点可将多种检测技术集成于微尺度中,为CTC的分离、鉴定和表征提供了一个高效的平台,有助于对肿瘤患者进行个体化分析与治疗。最近,三维(3D)打印技术的兴起为微流控芯片的制造提供了更高效、个性化的方式,避免了传统微流体器件制作方法步骤复杂、耗时等问题。逐层打印出的3D结构将促进微流控芯片实现更高效率和更高通量,并将推动实验室技术成功应用于临床,为肿瘤的生物学和临床研究开辟新视野,为乳腺癌的诊断治疗提供前所未有的机会。本文中,笔者分析了近年来CTC的不同检测手段的特点,阐述了微流控技术在乳腺癌CTC检测中的应用研究,以及3D打印微流控芯片技术前沿,并对3D打印微流控芯片技术在乳腺癌CTC检测中的应用前景进行了展望。

    Abstract:

    Breast cancer is the most common malignant tumor in women. Unpredictable metastatic relapse is a major reason for treatment failure, recurrence, and even death in breast cancer patients. Circulating tumor cells (CTCs) are defined as tumor cells that detach from the primary tumor and enter the circulatory or lymphatic system. Studies have confirmed that the detection of CTCs can provide important clinical information for the diagnosis, developing treatment strategies, and prognosis assessment of breast cancer. As one of the key targets for liquid biopsies, CTCs can be collected simply by extracting a patient's blood. However, most CTCs die in the circulation, with only a very small number surviving and invading distant organs. The scarcity in numbers, heterogeneity of CTCs, and interference from complex components in blood pose significant challenges to the accurate detection of CTCs. Various detection methods developed based on the biological and physical properties of CTCs often require separation and enrichment of CTCs before detection. However, preprocessing steps like adsorption, washing, and transfer inevitably result in CTC loss. Moreover, time-consuming, complex procedures, and expensive equipment further limit the clinical application of CTC detection. Therefore, there is an urgent need for the development of new detection technologies. Microfluidic technology, characterized by microfabricated structures, has received significant attention and research in recent years. Microfluidic technology allows for precise control of micrometer-scale fluids and cells, making it particularly suitable for detecting rare CTCs. Microfluidic chips offer advantages such as low cost, simplicity of operation, low consumables, high throughput, and real-time detection. Their miniaturization allows for the integration of various detection techniques into a micro-scale platform, providing an efficient platform for the isolation, identification, and characterization of CTCs, contributing to personalized analysis and treatment of cancer patients. Recently, the rise of three dimession (3D) printing technology has provided a more efficient and personalized approach to the fabrication of microfluidic chips, avoiding the complexities and time-consuming aspects of traditional microfluidic device production. Layer-by-layer printed 3D structures will promote higher efficiency and throughput of microfluidic chips, facilitating the successful application of laboratory techniques in clinical settings. This opens up new perspectives for biological and clinical research on tumors and offers unprecedented opportunities for the diagnosis and treatment of breast cancer. In this article, the authors analyze the characteristics of different CTC detection methods in recent years, elucidate the application of microfluidic technology in the detection of breast cancer CTCs, and the cutting-edge technology of 3D-printed microfluidic chips, and provide an outlook on the application prospects of 3D-printed microfluidic chips in the detection of CTCs in breast cancer.

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尉卓凡,宁智文,胡波,袁时芳.乳腺癌循环肿瘤细胞微流控芯片检测研究进展[J].中国普通外科杂志,2023,32(11):1804-1812.
DOI:10.7659/j. issn.1005-6947.2023.11.020

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  • 收稿日期:2023-04-30
  • 最后修改日期:2023-06-12
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  • 在线发布日期: 2023-12-15