Drug screening of biopsy-derived spheroids using a self-generated microfluidic concentration gradient

Theresa Mulholland, Milly McAllister, Samantha Patek, David Flint, Mark Underwood, Alexander Sim, Joanne Edwards, Michele Zagnoni

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Performing drug screening of tissue derived from cancer patient biopsies using physiologically relevant 3D tumour models presents challenges due to the limited amount of available cell material. Here, we present a microfluidic platform that enables drug screening of cancer cell-enriched multicellular spheroids derived from tumour biopsies, allowing extensive anticancer compound screening prior to treatment. This technology was validated using cell lines and then used to screen primary human prostate cancer cells, grown in 3D as a heterogeneous culture from biopsy-derived tissue. The technology enabled the formation of repeatable drug concentration gradients across an array of spheroids without external fluid actuation, delivering simultaneously a range of drug concentrations to multiple sized spheroids, as well as replicates for each concentration. As proof-of-concept screening, spheroids were generated from two patient biopsies and a panel of standard-of-care compounds for prostate cancer were tested. Brightfield and fluorescence images were analysed to provide readouts of spheroid growth and health, as well as drug efficacy over time. Overall, this technology could prove a useful tool for personalised medicine and future drug development, with the potential to provide cost- and time-reduction in the healthcare delivery.
LanguageEnglish
Article number14672
Number of pages12
JournalScientific Reports
Volume8
DOIs
Publication statusPublished - 2 Oct 2018

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Preclinical Drug Evaluations
Microfluidics
Biopsy
Screening
Technology
Pharmaceutical Preparations
Neoplasms
Prostatic Neoplasms
Cells
Cellular Spheroids
Precision Medicine
Tumors
Standard of Care
Tissue
Fluorescence
Bioelectric potentials
Delivery of Health Care
Cell culture
Costs and Cost Analysis
Cell Line

Keywords

  • drug screening
  • cancer patients
  • biopsy
  • microfluidic platform
  • anticancer compound screening

Cite this

Mulholland, Theresa ; McAllister, Milly ; Patek, Samantha ; Flint, David ; Underwood, Mark ; Sim, Alexander ; Edwards, Joanne ; Zagnoni, Michele. / Drug screening of biopsy-derived spheroids using a self-generated microfluidic concentration gradient. In: Scientific Reports. 2018 ; Vol. 8.
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abstract = "Performing drug screening of tissue derived from cancer patient biopsies using physiologically relevant 3D tumour models presents challenges due to the limited amount of available cell material. Here, we present a microfluidic platform that enables drug screening of cancer cell-enriched multicellular spheroids derived from tumour biopsies, allowing extensive anticancer compound screening prior to treatment. This technology was validated using cell lines and then used to screen primary human prostate cancer cells, grown in 3D as a heterogeneous culture from biopsy-derived tissue. The technology enabled the formation of repeatable drug concentration gradients across an array of spheroids without external fluid actuation, delivering simultaneously a range of drug concentrations to multiple sized spheroids, as well as replicates for each concentration. As proof-of-concept screening, spheroids were generated from two patient biopsies and a panel of standard-of-care compounds for prostate cancer were tested. Brightfield and fluorescence images were analysed to provide readouts of spheroid growth and health, as well as drug efficacy over time. Overall, this technology could prove a useful tool for personalised medicine and future drug development, with the potential to provide cost- and time-reduction in the healthcare delivery.",
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Drug screening of biopsy-derived spheroids using a self-generated microfluidic concentration gradient. / Mulholland, Theresa; McAllister, Milly; Patek, Samantha; Flint, David; Underwood, Mark; Sim, Alexander; Edwards, Joanne; Zagnoni, Michele.

In: Scientific Reports, Vol. 8, 14672, 02.10.2018.

Research output: Contribution to journalArticle

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