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Nano Research 2022, 15(5): 4357-4365 https://doi.org/10.1007/s12274-022-4100-5
Research Article | Issue | Published: 08 February 2022

2D profiling of tumor chemotactic and molecular phenotype at single cell resolution using a SERS-microfluidic chip

Show Author's Information Yizhi Zhang1,2,§,  Lei Wu1,§,  Kuo Yang1,  Shenfei Zong1,  Zhuyuan Wang1( ),  Yiping Cui1( )
Advanced Photonics Center, School of Electronic Science and Engineering, Southeast University, Nanjing 210096, China
Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China

§ Yizhi Zhang and Lei Wu contributed equally to this work.

Keywords:
microfluidic chip, gold@silver nanoparticles, surface enhanced Raman spectroscopy, single cell analysis, two-dimensional (2D) phenotype profiling
Topics:
Raman spectroscopy
Cite this article:
Zhang Y, Wu L, Yang K, et al. 2D profiling of tumor chemotactic and molecular phenotype at single cell resolution using a SERS-microfluidic chip. Nano Research, 2022, 15(5): 4357-4365. https://doi.org/10.1007/s12274-022-4100-5
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Abstract Full text Electronic supplementary material About this article

Emerging single-cell technologies create new opportunities for unraveling tumor heterogeneity. However, the development of high-content phenotyping platform is still at its infancy. Here, we develop a microfluidic chip for two-dimensional (2D) profiling of tumor chemotactic and molecular features at single cell resolution. Individual cells were captured by the triangular micropillar arrays in the cell-loading channel, facilitating downstream single-cell analysis. For 2D phenotyping, the chemotactic properties of tumor cells were visualized through cellular migratory behavior in microchannels, while their protein expression was profiled with multiplex surface enhanced Raman scattering (SERS) nanovectors, in which Raman reporter-embedded gold@silver core–shell nanoparticles (Au@Ag REPs) were modified with DNA aptamers targeting cellular surface proteins. As a proof of concept, breast cancer cells with diverse phenotypes were tested on the chip, demonstrating the capability of this platform for simultaneous chemotactic and molecular analysis. The chip is expected to provide a powerful tool for investigating tumor heterogeneity and promoting clinical precision medicine.


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Electronic supplementary material
About this article

2D profiling of tumor chemotactic and molecular phenotype at single cell resolution using a SERS-microfluidic chip

Show Author's information Yizhi Zhang1,2,§, Lei Wu1,§, Kuo Yang1, Shenfei Zong1, Zhuyuan Wang1( ), Yiping Cui1( )
Advanced Photonics Center, School of Electronic Science and Engineering, Southeast University, Nanjing 210096, China
Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing 211106, China

§ Yizhi Zhang and Lei Wu contributed equally to this work.

Abstract

Emerging single-cell technologies create new opportunities for unraveling tumor heterogeneity. However, the development of high-content phenotyping platform is still at its infancy. Here, we develop a microfluidic chip for two-dimensional (2D) profiling of tumor chemotactic and molecular features at single cell resolution. Individual cells were captured by the triangular micropillar arrays in the cell-loading channel, facilitating downstream single-cell analysis. For 2D phenotyping, the chemotactic properties of tumor cells were visualized through cellular migratory behavior in microchannels, while their protein expression was profiled with multiplex surface enhanced Raman scattering (SERS) nanovectors, in which Raman reporter-embedded gold@silver core–shell nanoparticles (Au@Ag REPs) were modified with DNA aptamers targeting cellular surface proteins. As a proof of concept, breast cancer cells with diverse phenotypes were tested on the chip, demonstrating the capability of this platform for simultaneous chemotactic and molecular analysis. The chip is expected to provide a powerful tool for investigating tumor heterogeneity and promoting clinical precision medicine.

Keywords: microfluidic chip, gold@silver nanoparticles, surface enhanced Raman spectroscopy, single cell analysis, two-dimensional (2D) phenotype profiling

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Publication history
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Acknowledgements

Publication history

Received: 26 September 2021
Revised: 17 December 2021
Accepted: 22 December 2021
Published: 08 February 2022
Issue date: May 2022

Copyright

© Tsinghua University Press 2022

Acknowledgements

Acknowledgements

This study was supported by the National Science Fund for Excellent Young Scholars (No. 61822503), the National Natural Science Foundation of China (Nos. 62175030 and 62175027), China Postdoctoral Science Foundation (No. 2021TQ0147), Jiangsu Innovation and Entrepreneurship Program (No. JSSCBS20210126), Nanjing Science and Technology Innovation Project for Returned Overseas Chinese Scholars (No. 1106000308), and the Fundamental Research Funds for the Central Universities (Nos. 3206002104D and 3206002108A1).

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