Label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites

Abstract The isolation of a patient's metastatic cancer cells is the first, enabling step toward treatment of that patient using modern personalized medicine techniques. Whereas traditional standard-of-care approaches select treatments for cancer patients based on the histological classificatio...

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Autores principales:	Nicholas E. Stone, Abhishek Raj, Katherine M. Young, Adam P. DeLuca, Fatima Ezahra Chrit, Budd A. Tucker, Alexander Alexeev, John McDonald, Benedict B. Benigno, Todd Sulchek
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0613c178092047e293ef608a8167e235
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spelling	oai:doaj.org-article:0613c178092047e293ef608a8167e2352021-12-02T14:58:46ZLabel-free microfluidic enrichment of cancer cells from non-cancer cells in ascites10.1038/s41598-021-96862-y2045-2322https://doaj.org/article/0613c178092047e293ef608a8167e2352021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96862-yhttps://doaj.org/toc/2045-2322Abstract The isolation of a patient's metastatic cancer cells is the first, enabling step toward treatment of that patient using modern personalized medicine techniques. Whereas traditional standard-of-care approaches select treatments for cancer patients based on the histological classification of cancerous tissue at the time of diagnosis, personalized medicine techniques leverage molecular and functional analysis of a patient's own cancer cells to select treatments with the highest likelihood of being effective. Unfortunately, the pure populations of cancer cells required for these analyses can be difficult to acquire, given that metastatic cancer cells typically reside in fluid containing many different cell populations. Detection and analyses of cancer cells therefore require separation from these contaminating cells. Conventional cell sorting approaches such as Fluorescence Activated Cell Sorting or Magnetic Activated Cell Sorting rely on the presence of distinct surface markers on cells of interest which may not be known nor exist for cancer applications. In this work, we present a microfluidic platform capable of label-free enrichment of tumor cells from the ascites fluid of ovarian cancer patients. This approach sorts cells based on differences in biomechanical properties, and therefore does not require any labeling or other pre-sort interference with the cells. The method is also useful in the cases when specific surface markers do not exist for cells of interest. In model ovarian cancer cell lines, the method was used to separate invasive subtypes from less invasive subtypes with an enrichment of ~ sixfold. In ascites specimens from ovarian cancer patients, we found the enrichment protocol resulted in an improved purity of P53 mutant cells indicative of the presence of ovarian cancer cells. We believe that this technology could enable the application of personalized medicine based on analysis of liquid biopsy patient specimens, such as ascites from ovarian cancer patients, for quick evaluation of metastatic disease progression and determination of patient-specific treatment.Nicholas E. StoneAbhishek RajKatherine M. YoungAdam P. DeLucaFatima Ezahra ChritBudd A. TuckerAlexander AlexeevJohn McDonaldBenedict B. BenignoTodd SulchekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicholas E. Stone Abhishek Raj Katherine M. Young Adam P. DeLuca Fatima Ezahra Chrit Budd A. Tucker Alexander Alexeev John McDonald Benedict B. Benigno Todd Sulchek Label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites
description	Abstract The isolation of a patient's metastatic cancer cells is the first, enabling step toward treatment of that patient using modern personalized medicine techniques. Whereas traditional standard-of-care approaches select treatments for cancer patients based on the histological classification of cancerous tissue at the time of diagnosis, personalized medicine techniques leverage molecular and functional analysis of a patient's own cancer cells to select treatments with the highest likelihood of being effective. Unfortunately, the pure populations of cancer cells required for these analyses can be difficult to acquire, given that metastatic cancer cells typically reside in fluid containing many different cell populations. Detection and analyses of cancer cells therefore require separation from these contaminating cells. Conventional cell sorting approaches such as Fluorescence Activated Cell Sorting or Magnetic Activated Cell Sorting rely on the presence of distinct surface markers on cells of interest which may not be known nor exist for cancer applications. In this work, we present a microfluidic platform capable of label-free enrichment of tumor cells from the ascites fluid of ovarian cancer patients. This approach sorts cells based on differences in biomechanical properties, and therefore does not require any labeling or other pre-sort interference with the cells. The method is also useful in the cases when specific surface markers do not exist for cells of interest. In model ovarian cancer cell lines, the method was used to separate invasive subtypes from less invasive subtypes with an enrichment of ~ sixfold. In ascites specimens from ovarian cancer patients, we found the enrichment protocol resulted in an improved purity of P53 mutant cells indicative of the presence of ovarian cancer cells. We believe that this technology could enable the application of personalized medicine based on analysis of liquid biopsy patient specimens, such as ascites from ovarian cancer patients, for quick evaluation of metastatic disease progression and determination of patient-specific treatment.
format	article
author	Nicholas E. Stone Abhishek Raj Katherine M. Young Adam P. DeLuca Fatima Ezahra Chrit Budd A. Tucker Alexander Alexeev John McDonald Benedict B. Benigno Todd Sulchek
author_facet	Nicholas E. Stone Abhishek Raj Katherine M. Young Adam P. DeLuca Fatima Ezahra Chrit Budd A. Tucker Alexander Alexeev John McDonald Benedict B. Benigno Todd Sulchek
author_sort	Nicholas E. Stone
title	Label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites
title_short	Label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites
title_full	Label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites
title_fullStr	Label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites
title_full_unstemmed	Label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites
title_sort	label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/0613c178092047e293ef608a8167e235
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Label-free microfluidic enrichment of cancer cells from non-cancer cells in ascites

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