Kashaninejad Navid, Nikmaneshi Mohammad Reza, Moghadas Hajar, Kiyoumarsi Oskouei Amir, Rismanian Milad, Barisam Maryam, Saidi Mohammad Said, Firoozabadi Bahar
School of Mechanical Engineering, Sharif University of Technology, 11155-9567 Tehran, Iran.
Micromachines (Basel). 2016 Jul 28;7(8):130. doi: 10.3390/mi7080130.
With a mortality rate over 580,000 per year, cancer is still one of the leading causes of death worldwide. However, the emerging field of microfluidics can potentially shed light on this puzzling disease. Unique characteristics of microfluidic chips (also known as micro-total analysis system) make them excellent candidates for biological applications. The ex vivo approach of tumor-on-a-chip is becoming an indispensable part of personalized medicine and can replace in vivo animal testing as well as conventional in vitro methods. In tumor-on-a-chip, the complex three-dimensional (3D) nature of malignant tumor is co-cultured on a microfluidic chip and high throughput screening tools to evaluate the efficacy of anticancer drugs are integrated on the same chip. In this article, we critically review the cutting edge advances in this field and mainly categorize each tumor-on-a-chip work based on its primary organ. Specifically, design, fabrication and characterization of tumor microenvironment; cell culture technique; transferring mechanism of cultured cells into the microchip; concentration gradient generators for drug delivery; in vitro screening assays of drug efficacy; and pros and cons of each microfluidic platform used in the recent literature will be discussed separately for the tumor of following organs: (1) Lung; (2) Bone marrow; (3) Brain; (4) Breast; (5) Urinary system (kidney, bladder and prostate); (6) Intestine; and (7) Liver. By comparing these microchips, we intend to demonstrate the unique design considerations of each tumor-on-a-chip based on primary organ, e.g., how microfluidic platform of lung-tumor-on-a-chip may differ from liver-tumor-on-a-chip. In addition, the importance of heart⁻liver⁻intestine co-culture with microvasculature in tumor-on-a-chip devices for in vitro chemosensitivity assay will be discussed. Such system would be able to completely evaluate the absorption, distribution, metabolism, excretion and toxicity (ADMET) of anticancer drugs and more realistically recapitulate tumor in vivo-like microenvironment.
癌症每年的死亡率超过58万，仍然是全球主要死因之一。然而，新兴的微流控领域有可能为这种令人困惑的疾病带来曙光。微流控芯片（也称为微全分析系统）的独特特性使其成为生物应用的理想选择。芯片上肿瘤的体外方法正成为个性化医疗中不可或缺的一部分，并且可以替代体内动物试验以及传统的体外方法。在芯片上肿瘤模型中，恶性肿瘤的复杂三维（3D）特性在微流控芯片上进行共培养，并且在同一芯片上集成了用于评估抗癌药物疗效的高通量筛选工具。在本文中，我们批判性地回顾了该领域的前沿进展，并主要根据其主要器官对每个芯片上肿瘤模型的研究进行分类。具体而言，将分别讨论以下器官肿瘤的微流控平台的设计、制造和表征；细胞培养技术；培养细胞向微芯片的转移机制；药物递送的浓度梯度发生器；药物疗效的体外筛选测定；以及近期文献中使用的每个微流控平台的优缺点：（1）肺；（2）骨髓；（3）脑；（4）乳腺；（5）泌尿系统（肾脏、膀胱和前列腺）；（6）肠道；（7）肝脏。通过比较这些微芯片，我们旨在展示基于主要器官的每个芯片上肿瘤模型的独特设计考虑因素，例如，肺芯片上肿瘤模型的微流控平台与肝芯片上肿瘤模型的微流控平台有何不同。此外，还将讨论在芯片上肿瘤模型装置中进行体外化学敏感性测定时，心脏-肝脏-肠道与微血管共培养的重要性。这样的系统将能够全面评估抗癌药物的吸收、分布、代谢、排泄和毒性（ADMET），并更真实地模拟体内肿瘤样微环境。
