Department of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan; Department of Radiation Oncology, Chang Gung Memorial Hospital, Linkou, Taiwan; Department of Electrical & Electronic Engineering, Yonsei University, Seoul, South Korea.
Department of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan.
Anal Chim Acta. 2024 Dec 15;1332:343371. doi: 10.1016/j.aca.2024.343371. Epub 2024 Oct 24.
Liver cancer stands as a leading cause of cancer-related deaths globally, challenging conventional treatments due to resistance to chemotherapy and targeted therapy. Although frontline medications show initial efficacy, prolonged use often leads to resistance and harm. Current clinical strategies rely on combination therapies, but evaluating their effectiveness remains challenging.
To address this, we developed a hydrogel-based diffusion microfluidic platform for assessing chemosensitivity. This platform features a hydrogel-filled diffusion layer linked to liquid wells, allowing the creation of drug gradients. Tumor spheroids, cultured on the non-adhesive hydrogel surface, were exposed to single or combination drug gradients. Analysis revealed that drug efficacy, quantified by IC values, could be determined from responses to single drug gradients. A novel method was introduced to assess spheroid circularity as a time-invariant index of drug efficacy. Furthermore, exposing spheroids to 2D combination drug gradients allowed intuitive visualization of their responses via a color map. This analysis identified optimal drug combinations, exhibiting superior efficacy to monotherapy.
The microfluidic platform enables assessment of synergistic effects and replicates in vivo conditions, enhancing the relevance of test results. By offering a streamlined, fast, and efficient drug screening approach, this platform aims to provide insight into tumor spheroid responses to varying drug combinations, facilitating more effective clinical applications.
肝癌是全球癌症相关死亡的主要原因，由于对化疗和靶向治疗的耐药性，对常规治疗方法构成挑战。虽然一线药物显示出初始疗效，但长期使用往往会导致耐药性和伤害。目前的临床策略依赖于联合治疗，但评估其疗效仍然具有挑战性。
为了解决这个问题，我们开发了一种基于水凝胶的扩散微流控平台，用于评估化疗敏感性。该平台具有一个充满水凝胶的扩散层，与液体井相连，允许创建药物梯度。肿瘤球体在非粘附水凝胶表面上培养，并暴露于单一或组合药物梯度下。分析表明，通过 IC 值来定量药物功效，可以从单一药物梯度的反应中确定。引入了一种新的方法来评估球体的圆度作为药物功效的时间不变指标。此外，通过暴露于 2D 组合药物梯度，通过颜色图直观地可视化球体的反应。这种分析确定了最佳的药物组合，表现出优于单药治疗的疗效。
该微流控平台能够评估协同作用，并复制体内条件，提高测试结果的相关性。通过提供一种简化、快速和高效的药物筛选方法，该平台旨在深入了解肿瘤球体对不同药物组合的反应，促进更有效的临床应用。
