芯片上活单细胞的时空多组学分析用于癌症治疗。

IF 9.1 1区 化学 Q1 CHEMISTRY, ANALYTICAL
Kunru Yu,Shengjie Chen,Rong Zhu
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引用次数: 0

摘要

单细胞分子谱分析已成为生物学研究的前沿技术,在阐明基本生命过程和细胞异质性方面发挥着关键作用。然而,传统方法通常提供终点测量,并且需要破坏细胞,这对长期监测活细胞事件(例如癌症治疗)提出了挑战。肿瘤治疗电场(Tumor Treating Fields, TTFields)是一种非侵入性治疗方式,通过在肿瘤区域施加低强度中频交变电场来抑制肿瘤生长和侵袭,其在肿瘤生理学中的分子机制尚不清楚。在这项研究中,我们提出了一种多功能微芯片,能够连续原位监测活单细胞的分子特征。该平台将空间细胞定位、单细胞多分子跟踪、表面增强拉曼散射(SERS)和TTFields处理功能集成在微芯片上。通过对TTFields和化疗药物治疗的肝癌细胞进行多重分析,我们实现了癌症治疗的时空多组学分析。与糖酵解、遗传稳定性和膜完整性相关的关键分子事件的时间跟踪显示,在接受和未接受TTFields治疗的组之间存在显著差异。分子图谱的因果网络分析揭示了TTFields调节致癌途径的潜在机制。我们的工作证明了所提出的微芯片平台实时监测活细胞分子动力学的有效性,为精确癌症治疗提供了有力的工具。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Spatial-Temporal Multiomics Profiling of Living Single Cells on Chip for Cancer Therapy.
Single-cell molecular profiling has emerged as a cutting-edge technology in biological research, playing a pivotal role in elucidating fundamental life processes and cellular heterogeneity. However, traditional methods generally provide end point measurements and require cell disruption, posing challenges for long-term monitoring of living cell events, e.g., cancer therapy. Tumor Treating Fields (TTFields), a noninvasive therapeutic modality, exert inhibitory effects on tumor growth and invasion by applying low-intensity intermediate-frequency alternating electric fields to tumor regions, whose molecular mechanism on cancer physiology remains poorly understood. In this study, we propose a multifunctional microchip capable of continuous in situ monitoring of molecular signatures in living single cells. The platform integrates spatial cell positioning, single-cellular multimolecule tracking with surface-enhanced Raman scattering (SERS), and TTFields treatment functionalities on a microchip. Using multiplexed analysis of liver cancer cells treated with TTFields and chemotherapy drugs, we implement spatial-temporal multiomics profiling for cancer therapy. Temporal tracking of critical molecular events associated with glycolysis, genetic stability, and membrane integrity reveals significant differences between the groups with and without TTFields treatment. Causal network analysis of molecular profiles uncovers the underlying mechanisms through which TTFields modulate oncogenic pathways. Our work demonstrates the effectiveness of the proposed microchip platform for real-time monitoring of living cell molecular dynamics, offering a powerful tool for precision cancer therapy.
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来源期刊
ACS Sensors
ACS Sensors Chemical Engineering-Bioengineering
CiteScore
14.50
自引率
3.40%
发文量
372
期刊介绍: ACS Sensors is a peer-reviewed research journal that focuses on the dissemination of new and original knowledge in the field of sensor science, particularly those that selectively sense chemical or biological species or processes. The journal covers a broad range of topics, including but not limited to biosensors, chemical sensors, gas sensors, intracellular sensors, single molecule sensors, cell chips, and microfluidic devices. It aims to publish articles that address conceptual advances in sensing technology applicable to various types of analytes or application papers that report on the use of existing sensing concepts in new ways or for new analytes.
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