A Microfluidic Chip for Efficient Circulating Tumor Cells Enrichment, Screening, and Single‐Cell RNA Sequencing

Single‐cell RNA sequencing on circulating tumor cells (CTCs) proves useful to study mechanisms of tumor heterogeneity, metastasis, and drug resistance. Currently, single‐cell RNA sequencing of CTCs usually takes three prerequisite steps: enrichment of CTCs from whole blood, characterization of captu...

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Bibliographic Details
Published in:Proteomics (Weinheim) 2021-02, Vol.21 (3-4), p.e2000060-n/a
Main Authors: Shi, Fanghao, Jia, Fei, Wei, Zewen, Ma, Yan, Fang, Zhiguo, Zhang, Weikai, Hu, Zhiyuan
Format: Article
Language:English
Subjects:
Blood
Blood coagulation
circulating tumor cells
Drug resistance
Enrichment
Gene expression
Gene sequencing
Heterogeneity
Lysis
Metastases
microfluidic chip
Microfluidics
Micromanipulation
Ribonucleic acid
RNA
single‐cell RNA sequencing
Target recognition
Tumor cells
Tumors
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Summary:Single‐cell RNA sequencing on circulating tumor cells (CTCs) proves useful to study mechanisms of tumor heterogeneity, metastasis, and drug resistance. Currently, single‐cell RNA sequencing of CTCs usually takes three prerequisite steps: enrichment of CTCs from whole blood, characterization of captured cells by immunostaining and microscopic imaging, and single‐cell isolation through micromanipulation. However, multiple pipetting and transferring steps can easily cause the loss of rare CTCs. To address this issue, a novel integrated microfluidic chip for sequential enrichment, isolation, and characterization of CTCs at single‐cell level, is developed. And, single CTC lysis is achieved on the same chip. The microfluidic chip includes functions of blood clot filtration, single‐cell isolation, identification, and target single‐cell lysate collection. By spiking tumor cells into whole blood, it is validated that this microfluidic chip can effectively conduct single‐cell CTCs RNA sequencing. The approach lays a solid foundation for the analysis of RNA expression profiling of single‐cell CTCs.
ISSN:1615-9853
1615-9861
DOI:10.1002/pmic.202000060