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A microfluidics platform for combinatorial drug screening on cancer biopsies

Screening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing...

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Autores principales: Eduati, Federica, Utharala, Ramesh, Madhavan, Dharanija, Neumann, Ulf Peter, Longerich, Thomas, Cramer, Thorsten, Saez-Rodriguez, Julio, Merten, Christoph A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015045/
https://www.ncbi.nlm.nih.gov/pubmed/29934552
http://dx.doi.org/10.1038/s41467-018-04919-w
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author Eduati, Federica
Utharala, Ramesh
Madhavan, Dharanija
Neumann, Ulf Peter
Longerich, Thomas
Cramer, Thorsten
Saez-Rodriguez, Julio
Merten, Christoph A.
author_facet Eduati, Federica
Utharala, Ramesh
Madhavan, Dharanija
Neumann, Ulf Peter
Longerich, Thomas
Cramer, Thorsten
Saez-Rodriguez, Julio
Merten, Christoph A.
author_sort Eduati, Federica
collection PubMed
description Screening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing the plug composition on demand and enable collecting >1200 data points (56 different conditions with at least 20 replicates each) per biopsy. After deriving and validating efficient and specific drug combinations for two genetically different pancreatic cancer cell lines and xenograft mouse models, we additionally screen live cells from human solid tumours with no need for ex vivo culturing steps, and obtain highly specific sensitivity profiles. The entire workflow can be completed within 48 h at assay costs of less than US$ 150 per patient. We believe this can pave the way for rapid determination of optimal personalized cancer therapies.
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spelling pubmed-60150452018-06-25 A microfluidics platform for combinatorial drug screening on cancer biopsies Eduati, Federica Utharala, Ramesh Madhavan, Dharanija Neumann, Ulf Peter Longerich, Thomas Cramer, Thorsten Saez-Rodriguez, Julio Merten, Christoph A. Nat Commun Article Screening drugs on patient biopsies from solid tumours has immense potential, but is challenging due to the small amount of available material. To address this, we present here a plug-based microfluidics platform for functional screening of drug combinations. Integrated Braille valves allow changing the plug composition on demand and enable collecting >1200 data points (56 different conditions with at least 20 replicates each) per biopsy. After deriving and validating efficient and specific drug combinations for two genetically different pancreatic cancer cell lines and xenograft mouse models, we additionally screen live cells from human solid tumours with no need for ex vivo culturing steps, and obtain highly specific sensitivity profiles. The entire workflow can be completed within 48 h at assay costs of less than US$ 150 per patient. We believe this can pave the way for rapid determination of optimal personalized cancer therapies. Nature Publishing Group UK 2018-06-22 /pmc/articles/PMC6015045/ /pubmed/29934552 http://dx.doi.org/10.1038/s41467-018-04919-w Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Eduati, Federica
Utharala, Ramesh
Madhavan, Dharanija
Neumann, Ulf Peter
Longerich, Thomas
Cramer, Thorsten
Saez-Rodriguez, Julio
Merten, Christoph A.
A microfluidics platform for combinatorial drug screening on cancer biopsies
title A microfluidics platform for combinatorial drug screening on cancer biopsies
title_full A microfluidics platform for combinatorial drug screening on cancer biopsies
title_fullStr A microfluidics platform for combinatorial drug screening on cancer biopsies
title_full_unstemmed A microfluidics platform for combinatorial drug screening on cancer biopsies
title_short A microfluidics platform for combinatorial drug screening on cancer biopsies
title_sort microfluidics platform for combinatorial drug screening on cancer biopsies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6015045/
https://www.ncbi.nlm.nih.gov/pubmed/29934552
http://dx.doi.org/10.1038/s41467-018-04919-w
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