Phage-Based Profiling of Rare Single Cells Using Nanoparticle-Directed Capture

Yuan Ma, Kangfu Chen, Fan Xia, Randy Atwal, Hansen Wang, Sharif U. Ahmed, Lia Cardarelli, Irene Lui, Bill Duong, Zongjie Wang, James A. Wells, Sachdev S. Sidhu, Shana O. Kelley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Advances in single-cell level profiling of the proteome require quantitative and versatile platforms, especially for rare cell analyses such as circulating tumor cell (CTC) profiling. Here we demonstrate an integrated microfluidic chip that uses magnetic nanoparticles to capture single tumor cells with high efficiency, permits on-chip incubation, and facilitates in situ cell-surface protein expression analysis. Combined with phage-based barcoding and next-generation sequencing technology, we were able to monitor changes in the expression of multiple surface markers stimulated in response to CTC adherence. Interestingly, we found fluctuations in the expression of Frizzled2 (FZD2) that reflected the microenvironment of the single cells. This platform has a high potential for in-depth screening of multiple surface antigens simultaneously in rare cells with single-cell resolution, which will provide further insights regarding biological heterogeneity and human disease.

Original languageEnglish (US)
Pages (from-to)19202-19210
Number of pages9
JournalACS nano
Volume15
Issue number12
DOIs
StatePublished - Dec 28 2021
Externally publishedYes

Keywords

  • barcoded phage-displayed antibody screening
  • circulating tumor cells
  • microfluidics
  • phage-based profiling
  • protein expression
  • single cell

ASJC Scopus subject areas

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

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