A microfluidics platform for combinatorial drug screening on cancer biopsies

Federica Eduati; Ramesh Utharala; Dharanija Madhavan; Ulf Peter Neumann; Thomas Longerich; Thorsten Cramer; Julio Saez-Rodriguez; Christoph A. Merten

doi:10.1038/s41467-018-04919-w

A microfluidics platform for combinatorial drug screening on cancer biopsies

Federica Eduati, Ramesh Utharala, Dharanija Madhavan, Ulf Peter Neumann, Thomas Longerich, Thorsten Cramer, Julio Saez-Rodriguez^*, Christoph A. Merten^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	2434
Number of pages	13
Journal	Nature Communications
Volume	9
DOIs	https://doi.org/10.1038/s41467-018-04919-w
Publication status	Published - 22 Jun 2018

Keywords

DROPLET-BASED MICROFLUIDICS
DUCTAL PANCREATIC-CANCER
EMBRYONIC STEM-CELLS
LUNG-CANCER
THERAPY
SENSITIVITY
MEDICINE
GROWTH
GENERATION
RESISTANCE

Access to Document

10.1038/s41467-018-04919-wLicence: CC BY

Cite this

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title = "A microfluidics platform for combinatorial drug screening on cancer biopsies",

abstract = "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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author = "Federica Eduati and Ramesh Utharala and Dharanija Madhavan and Neumann, {Ulf Peter} and Thomas Longerich and Thorsten Cramer and Julio Saez-Rodriguez and Merten, {Christoph A.}",

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T1 - A microfluidics platform for combinatorial drug screening on cancer biopsies

AU - Eduati, Federica

AU - Utharala, Ramesh

AU - Madhavan, Dharanija

AU - Neumann, Ulf Peter

AU - Longerich, Thomas

AU - Cramer, Thorsten

AU - Saez-Rodriguez, Julio

AU - Merten, Christoph A.

PY - 2018/6/22

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N2 - 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.

AB - 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.

KW - DROPLET-BASED MICROFLUIDICS

KW - DUCTAL PANCREATIC-CANCER

KW - EMBRYONIC STEM-CELLS

KW - LUNG-CANCER

KW - THERAPY

KW - SENSITIVITY

KW - MEDICINE

KW - GROWTH

KW - GENERATION

KW - RESISTANCE

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DO - 10.1038/s41467-018-04919-w

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JO - Nature Communications

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