Departments of Biomedical Engineering and Pathology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, China.
Departments of Biomedical Engineering and Pathology, School of Basic Medical Science, Central South University, Changsha, Hunan, 410013, China; Department of Bioengineering, School of Food and Bioengineering, Xuzhou University of Technology, Xuzhou, 221018, China.
Anal Chim Acta. 2024 Nov 22;1330:343278. doi: 10.1016/j.aca.2024.343278. Epub 2024 Sep 25.
Three-dimensional (3D) tumor microdevices are promising platform for biomimetic antitumor prediction and high-throughput chemotherapeutic screening and play crucial roles in the exploration of cancer-associated pharmaceutics and therapeutics. Traditional cell manipulation tools (e.g., non-adhesive surfaces and hanging drops) and recent microengineered systems (e.g., microfluidic chips and micropatterned array chips) have progressed in terms of microscale control, substantial tumor production, programmable drug combinations, and throughput analysis. However, establishing a facile 3D tumor microdevice to construct heterotypic tumor-microenvironmental profiles and for throughput, implementable, multi-instrument-compatible analysis of chemotherapies to advance consumer-grade tumor modelling tools is still being explored.
In this study, we present a facilely operated tumor-on-a-chip platform for massive production of heterotypic 3D tumors and diverse investigations of combinatorial chemotherapy screening. Large quantity of heterotypic tumor generation with high geometric controllability (size difference: 19.6 μm) and operational repeatability (n = 10) was achieved using simple-to-fabricate micropatterned chips. Multiple characteristics of solid tumors, including phenotypic gradients (viability and proliferation) and heterogeneous cellular compositions (multi-cell participation and stroma composition), were reproduced in heterotypic tumors, being more biomimetic than homotypic tumors. We completed the user-friendly analytical evaluation of individual and combinatorial drug therapies, and demonstrated the high applicability of the platform in biomimetic tumor-related large-scale manipulation and on-chip analysis, as well as its high compatibility for off-chip detection. The entire operative process during tumor production and chemotherapy only requires the routine and easy-to-master pipetting manipulation.
The establishment of a biomimetic and easy-to-use 3D tumor platform and the large-scale screening-like evaluation of combinatorial chemotherapies based on the usage of the micropatterned chip was achieved in a user-friendly manner. This advancement has significant application potential in the fields of oncology, drug discovery, and tissue engineering, and is expected to be valuable for developing accessible and generalizable tumor-on-a-chip microsystems for exploring cancer therapies.
三维（3D）肿瘤微器件是仿生抗肿瘤预测和高通量化疗筛选的有前途的平台，在癌症相关药物和治疗的探索中发挥着至关重要的作用。传统的细胞操作工具（例如非粘附表面和悬滴）和最近的微工程系统（例如微流控芯片和微图案阵列芯片）在微尺度控制、大量肿瘤生成、可编程药物组合和高通量分析方面取得了进展。然而，建立一个简单的 3D 肿瘤微器件来构建异质肿瘤-微环境图谱，并进行高通量、可实现的、多仪器兼容的化疗分析，以推进消费级肿瘤建模工具的发展，仍在探索之中。
在本研究中，我们提出了一种简单操作的肿瘤芯片平台，用于大量生成异质 3D 肿瘤，并对组合化疗筛选进行多样化研究。使用简单制造的微图案芯片可实现具有高几何可控性（尺寸差异：19.6μm）和操作可重复性（n=10）的大量异质肿瘤生成。异质肿瘤再现了多种实体瘤的特征，包括表型梯度（活力和增殖）和异质细胞组成（多细胞参与和基质组成），比同质肿瘤更具仿生特性。我们完成了对个体和组合药物治疗的用户友好型分析评估，并证明了该平台在仿生肿瘤相关的大规模操作和芯片上分析中的高适用性，以及其对离芯片检测的高兼容性。在肿瘤生成和化疗过程中的整个操作过程仅需要常规且易于掌握的移液操作。
以用户友好的方式实现了基于微图案芯片使用的仿生且易于使用的 3D 肿瘤平台的建立以及组合化疗的大规模筛选式评估。这一进展在肿瘤学、药物发现和组织工程等领域具有重要的应用潜力，有望为开发可访问和可推广的用于探索癌症疗法的肿瘤芯片微系统提供有价值的参考。
