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

doi:10.1021/acsnano.1c03935

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 journal › Article › peer-review

2 Scopus citations

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 language	English (US)
Pages (from-to)	19202-19210
Number of pages	9
Journal	ACS nano
Volume	15
Issue number	12
DOIs	https://doi.org/10.1021/acsnano.1c03935
State	Published - Dec 28 2021
Externally published	Yes

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)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1021/acsnano.1c03935

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@article{159b30499a17454dad088eec748cb481,

title = "Phage-Based Profiling of Rare Single Cells Using Nanoparticle-Directed Capture",

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.",

keywords = "barcoded phage-displayed antibody screening, circulating tumor cells, microfluidics, phage-based profiling, protein expression, single cell",

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

note = "Funding Information: We acknowledge the support of this research by the Canadian Institutes of Health Research (Foundation Grant to S.O.K.), the Natural Sciences and Engineering Research Council (Discovery Grant to S.O.K.), and the Canada First Research Excellence Fund (Medicine by Design Cycle 2 award). Publisher Copyright: {\textcopyright} 2021 American Chemical Society.",

year = "2021",

month = dec,

day = "28",

doi = "10.1021/acsnano.1c03935",

language = "English (US)",

volume = "15",

pages = "19202--19210",

journal = "ACS Nano",

issn = "1936-0851",

publisher = "American Chemical Society",

number = "12",

}

TY - JOUR

T1 - Phage-Based Profiling of Rare Single Cells Using Nanoparticle-Directed Capture

AU - Ma, Yuan

AU - Chen, Kangfu

AU - Xia, Fan

AU - Atwal, Randy

AU - Wang, Hansen

AU - Ahmed, Sharif U.

AU - Cardarelli, Lia

AU - Lui, Irene

AU - Duong, Bill

AU - Wang, Zongjie

AU - Wells, James A.

AU - Sidhu, Sachdev S.

AU - Kelley, Shana O.

N1 - Funding Information: We acknowledge the support of this research by the Canadian Institutes of Health Research (Foundation Grant to S.O.K.), the Natural Sciences and Engineering Research Council (Discovery Grant to S.O.K.), and the Canada First Research Excellence Fund (Medicine by Design Cycle 2 award). Publisher Copyright: © 2021 American Chemical Society.

PY - 2021/12/28

Y1 - 2021/12/28

N2 - 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.

AB - 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.

KW - barcoded phage-displayed antibody screening

KW - circulating tumor cells

KW - microfluidics

KW - phage-based profiling

KW - protein expression

KW - single cell

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ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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