期刊
MICROSYSTEMS & NANOENGINEERING
卷 8, 期 1, 页码 -出版社
SPRINGERNATURE
DOI: 10.1038/s41378-021-00342-2
关键词
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资金
- National Natural Science Foundation of China (NSFC) [22077079, 31971327, 81871448]
- Project of the National Innovation Special Zone
- Shanghai Municipal Science and Technology [2017SHZDZX01, 17DZ2203400, 18430760500]
- Shanghai Agriculture Applied Technology Development Program [G20180101]
- Shanghai Municipal Education Commission [ZXWF082101]
- National Key Research and Development Program of China [2017ZX10203205-006-002]
- Shanghai Jiao Tong University Biomedical Interdisciplinary Program [19x190020154, ZH2018ZDA01, YG2016QN24, YG2016MS60]
- Medical-Engineering Cross Foundation of Shanghai Jiao Tong University [ZH2018QNA54, ZH2018QNA49]
- Innovation Group Project of the Shanghai Municipal Health Commission [2019CXJQ03]
- Shanghai Clinical Medical Research Center [19MC1910800]
- third batch of industrialization projects of the Innovation Incubation Fund of Nantong and Shanghai Jiao Tong University [SD0820016]
- Oceanic Interdisciplinary Program of Shanghai Jiao Tong University [SL2020MS026]
- Shanghai Jiao Tong University [Agri-X20200101]
- SJTU Global Strategic Partnership Fund (2020 SJTU-HUJI)
- AEMD SJTU
In this study, an integrated multifunctional microfluidic system for highly efficient and label-free CTC isolation, enrichment, and single-cell immunoblotting (ieSCI) was developed. The system successfully identified a subgroup of cells that traditional bulk analysis could not detect and demonstrated its clinical application in breast cancer patients.
Effective capture and analysis of a single circulating tumor cell (CTC) is instrumental for early diagnosis and personalized therapy of tumors. However, due to their extremely low abundance and susceptibility to interference from other cells, high-throughput isolation, enrichment, and single-cell-level functional protein analysis of CTCs within one integrated system remains a major challenge. Herein, we present an integrated multifunctional microfluidic system for highly efficient and label-free CTC isolation, CTC enrichment, and single-cell immunoblotting (ieSCI). The ieSCI-chip is a multilayer microfluidic system that combines an inertia force-based cell sorter with a membrane filter for label-free CTC separation and enrichment and a thin layer of a photoactive polyacrylamide gel with microwell arrays at the bottom of the chamber for single-cell immunoblotting. The ieSCI-chip successfully identified a subgroup of apoptosis-negative (Bax-negative) cells, which traditional bulk analysis did not detect, from cisplatin-treated cells. Furthermore, we demonstrated the clinical application of the ieSCI-chip with blood samples from breast cancer patients for personalized CTC epithelial-to-mesenchymal transition (EMT) analysis. The expression level of a tumor cell marker (EpCAM) can be directly determined in isolated CTCs at the single-cell level, and the therapeutic response to anticancer drugs can be simultaneously monitored. Therefore, the ieSCI-chip provides a promising clinical translational tool for clinical drug response monitoring and personalized regimen development.
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