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Microfluidics-assisted multiplexed biomarker detection for in situ mapping of immune cells in tumor sections


Migliozzi, Daniel; Pelz, Benjamin; Dupouy, Diego G; Leblond, Anne-Laure; Soltermann, Alex; Gijs, Martin A M (2019). Microfluidics-assisted multiplexed biomarker detection for in situ mapping of immune cells in tumor sections. Microsystems & Nanoengineering (Online), 5:59.

Abstract

Because of the close interaction between tumors and the immune system, immunotherapies are nowadays considered as the most promising treatment against cancer. In order to define the diagnosis and the subsequent therapy, crucial information about the immune cells at the tumor site is needed. Indeed, different types or activation status of cells may be indicative for specific and personalized treatments. Here, we present a quantitative method to identify ten different immuno-markers in the same tumor cut section, thereby saving precious samples and enabling correlative analysis on several cell families and their activation status in a tumor microenvironment context. We designed and fabricated a microfluidic chip with optimal thermomechanical and optical properties for fast delivery of reagents on tissue slides and for fully automatic imaging by integration with an optical microscope. The multiplexing capability of the system is enabled by an optimized cyclic immunofluorescence protocol, with which we demonstrated quantitative sequential immunostaining of up to ten biomarkers on the same tissue section. Furthermore, we developed high-quality image-processing algorithms to map each cell in the entire tissue. As proof-of-concept analyses, we identified coexpression and colocalization patterns of biomarkers to classify the immune cells and their activation status. Thanks to the quantitativeness and the automation of both the experimental and analytical methods, we believe that this multiplexing approach will meet the increasing clinical need of personalized diagnostics and therapy in cancer pathology.

Abstract

Because of the close interaction between tumors and the immune system, immunotherapies are nowadays considered as the most promising treatment against cancer. In order to define the diagnosis and the subsequent therapy, crucial information about the immune cells at the tumor site is needed. Indeed, different types or activation status of cells may be indicative for specific and personalized treatments. Here, we present a quantitative method to identify ten different immuno-markers in the same tumor cut section, thereby saving precious samples and enabling correlative analysis on several cell families and their activation status in a tumor microenvironment context. We designed and fabricated a microfluidic chip with optimal thermomechanical and optical properties for fast delivery of reagents on tissue slides and for fully automatic imaging by integration with an optical microscope. The multiplexing capability of the system is enabled by an optimized cyclic immunofluorescence protocol, with which we demonstrated quantitative sequential immunostaining of up to ten biomarkers on the same tissue section. Furthermore, we developed high-quality image-processing algorithms to map each cell in the entire tissue. As proof-of-concept analyses, we identified coexpression and colocalization patterns of biomarkers to classify the immune cells and their activation status. Thanks to the quantitativeness and the automation of both the experimental and analytical methods, we believe that this multiplexing approach will meet the increasing clinical need of personalized diagnostics and therapy in cancer pathology.

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Additional indexing

Item Type:Journal Article, not_refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Physical Sciences > Atomic and Molecular Physics, and Optics
Physical Sciences > Materials Science (miscellaneous)
Physical Sciences > Condensed Matter Physics
Physical Sciences > Industrial and Manufacturing Engineering
Physical Sciences > Electrical and Electronic Engineering
Language:English
Date:2019
Deposited On:13 Jan 2020 09:59
Last Modified:11 May 2020 19:21
Publisher:Nature Publishing Group
ISSN:2055-7434
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1038/s41378-019-0104-z
PubMed ID:31700674

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