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Dong Z, Yan S, Liu B, et al. Single Living Cell Analysis Nanoplatform for High-Throughput Interrogation of Gene Mutation and Cellular Behavior. Nano Lett. 2021;21(11):4878-4886doi: 10.1021/acs.nanolett.1c00199.
Dong, Z., Yan, S., Liu, B., Hao, Y., Lin, L., Chang, T., Sun, H., Wang, Y., Li, H., Wu, H., Hang, X., He, S., Hu, J., Xue, X., Wu, N., & Chang, L. (2021). Single Living Cell Analysis Nanoplatform for High-Throughput Interrogation of Gene Mutation and Cellular Behavior. Nano letters, 21(11), 4878-4886. https://doi.org/10.1021/acs.nanolett.1c00199
Dong, Zaizai, et al. "Single Living Cell Analysis Nanoplatform for High-Throughput Interrogation of Gene Mutation and Cellular Behavior." Nano letters vol. 21,11 (2021): 4878-4886. doi: https://doi.org/10.1021/acs.nanolett.1c00199
Dong Z, Yan S, Liu B, Hao Y, Lin L, Chang T, Sun H, Wang Y, Li H, Wu H, Hang X, He S, Hu J, Xue X, Wu N, Chang L. Single Living Cell Analysis Nanoplatform for High-Throughput Interrogation of Gene Mutation and Cellular Behavior. Nano Lett. 2021 Jun 09;21(11):4878-4886. doi: 10.1021/acs.nanolett.1c00199. Epub 2021 Apr 08. PMID: 33830766.
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Nano Lett. 2021 Jun 09;21(11):4878-4886. doi: 10.1021/acs.nanolett.1c00199. Epub 2021 Apr 08.

Single Living Cell Analysis Nanoplatform for High-Throughput Interrogation of Gene Mutation and Cellular Behavior.

Nano letters

Zaizai Dong, Shi Yan, Bing Liu, Yongcun Hao, Long Lin, Tianrui Chang, Hong Sun, Yusen Wang, Hu Li, Han Wu, Xinxin Hang, Shiqi He, Jiaming Hu, Xinying Xue, Nan Wu, Lingqian Chang

Affiliations

  1. Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing 100191, China.
  2. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Thoracic Surgery II, Peking University Cancer Hospital & Institute, Beijing 100142, China.
  3. Ministry of Education Key Laboratory of Micro and Nano Systems for Aerospace, Northwestern Polytechnical University, Xi'an 710072, China.
  4. MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, Guangdong Provincial Key Laboratory of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510631, China.
  5. Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University, Peking University Ninth School of Clinical Medicine, Beijing 100038, China.
  6. Department of Respiratory and Critical Care, Chinese PLA General Hospital, Beijing 100853, China.
  7. Affiliated Hospital of Weifang Medical University, Shandong 261031, China.

PMID: 33830766 DOI: 10.1021/acs.nanolett.1c00199

Abstract

The genetic heterogeneities in cancer cells pose challenges to achieving precise drug treatment in a widely applicable manner. Most single-cell gene analysis methods rely on cell lysis for gene extraction and identification, showing limited capacity to provide the correlation of genetic properties and real-time cellular behaviors. Here, we report a single living cell analysis nanoplatform that enables interrogating gene properties and drug resistance in millions of single cells. We designed a Domino-probe to identify intracellular target RNAs while releasing 10-fold amplified fluorescence signals. An on-chip addressable microwell-nanopore array was developed for enhanced electro-delivery of the Domino-probe and in situ observation of cell behaviors. The proof-of-concept of the system was validated in primary lung cancer cell samples, revealing the positive-correlation of the ratio of EGFR mutant cells with their drug susceptibilities. This platform provides a high-throughput yet precise tool for exploring the relationship between intracellular genes and cell behaviors at the single-cell level.

Keywords: Domino-probe; gene mutation; lung cancer; nanochip; single-cell analysis

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