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3D肿瘤培养中的高通量阻抗监测:用于药物筛选的多重、无微流控平台。

High-throughput impedance monitoring in 3D tumor cultures: a multiplex, microfluidic-free platform for drug screening.

作者信息

Marino Attilio, Ziaja Kamil, Lefevre Marie Celine, Ceccarelli Maria Cristina, Battaglini Matteo, Filippeschi Carlo, Ciofani Gianni

机构信息

Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy.

Scuola Superiore Sant'Anna, The Biorobotics Institute, Viale Rinaldo Piaggio 34, 56025 Pontedera, Italy.

出版信息

Lab Chip. 2025 Jul 28. doi: 10.1039/d5lc00540j.

Abstract

The development of an effective therapy against glioblastoma (GBM) remains a significant and unmet clinical need. To address this challenge, creating predictive, physiologically relevant screening models is essential for accelerating the identification of promising drug candidates. In this paper, we present a novel impedance-based device where two-photon polymerization-fabricated scaffolds embedding electrodes are colonized by GBM cells, effectively replicating the three-dimensional environment of the microscopic tumor foci that persist following tumor resection and cause recurrence. The results demonstrated that the proposed GBM-on-chip model enables high-throughput, multiplexed, and real-time monitoring of the development of tumor spheroids and their responses to therapeutic agents. Validation studies demonstrated the platform ability to detect subtle cytotoxic effects undetectable by traditional immunofluorescence methods, with optical transparency enabling complementary imaging analysis. This system represents a versatile framework for assessing drug efficacy in complex, physiologically relevant 3D tumor models, paving the way for innovations in cancer pharmacology.

摘要

开发一种有效的胶质母细胞瘤(GBM)治疗方法仍然是一项重大且未得到满足的临床需求。为应对这一挑战,创建具有预测性、生理相关性的筛选模型对于加速识别有前景的候选药物至关重要。在本文中,我们展示了一种基于阻抗的新型装置,通过双光子聚合制造的嵌入电极的支架被GBM细胞定植,有效地复制了肿瘤切除后持续存在并导致复发的微观肿瘤病灶的三维环境。结果表明,所提出的芯片上GBM模型能够对肿瘤球体的生长及其对治疗药物的反应进行高通量、多参数和实时监测。验证研究表明,该平台能够检测到传统免疫荧光方法无法检测到的细微细胞毒性作用,其光学透明性使得能够进行互补成像分析。该系统代表了一个用于评估复杂、生理相关的三维肿瘤模型中药物疗效的通用框架,为癌症药理学的创新铺平了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/554b/12302074/ea0f58f1e1c7/d5lc00540j-f1.jpg

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