{"title":"芯片上活单细胞的时空多组学分析用于癌症治疗。","authors":"Kunru Yu,Shengjie Chen,Rong Zhu","doi":"10.1021/acssensors.5c01502","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":24,"journal":{"name":"ACS Sensors","volume":"22 1","pages":""},"PeriodicalIF":9.1000,"publicationDate":"2025-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Spatial-Temporal Multiomics Profiling of Living Single Cells on Chip for Cancer Therapy.\",\"authors\":\"Kunru Yu,Shengjie Chen,Rong Zhu\",\"doi\":\"10.1021/acssensors.5c01502\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"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.\",\"PeriodicalId\":24,\"journal\":{\"name\":\"ACS Sensors\",\"volume\":\"22 1\",\"pages\":\"\"},\"PeriodicalIF\":9.1000,\"publicationDate\":\"2025-10-12\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Sensors\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://doi.org/10.1021/acssensors.5c01502\",\"RegionNum\":1,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ANALYTICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Sensors","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acssensors.5c01502","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
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.
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.