A microfluidic platform for functional assays on tumour biopsy-derived spheroids for precision medicine

  • Theresa Mulholland

Student thesis: Doctoral Thesis

Abstract

Precision medicine aims to determine the ideal treatment for each cancer patient through the use of genomic and molecular diagnostics, as well as functional chemo-sensitivity screening assays. In recent years, the use and development of physiologically relevant patient-derived 3D in vitro cancer models has increased, since 3D ex vivo and in vitro models can replicate many aspects of the tumour microenvironment closely. These aim to provide more predictive tools than cell line-derived models for testing anticancer drug efficacy, particularly in the context of precision medicine in oncology. However, the small number of cells contained in many biopsies, especially in fine needle aspirates, is a major barrier to the use of patient biopsy tissue in 3D functional assays for precision medicine.;Microfluidic technologies have extensive miniaturisation capabilities, which offer increased data throughput while using very small amounts of cells. Therefore, this technology is a good candidate to perform 3D functional assays using patient-derived tissue. However, microfluidic devices frequently require an experienced handler or the use of dedicated fluid actuation equipment, which can create obstacles to its widespread adoption for precision medicine applications.;This PhD aimed to address these issues by creating a microfluidic platform and protocols for medium-throughput screening of tumour biopsy-derived spheroids. The microfluidic system developed in this PhD was used to generate thousands of spheroids from single cell suspensions, which could be cultured in the device for a prolonged period of time. Subsequently, as a proof-of-concept application, prostate biopsy-derived spheroids were exposed to drug concentration gradients, which allowed the establishment of one concentration-response curve per chip, and up to 21 concentration-response curves per patient. This platform offers a novel solution for the functional chemosensitivity testing of biopsy-derived spheroids, maximising the number of conditions that can be tested on patient-derived tissue for the purpose of precision medicine.
Date of Award2 Feb 2021
Original languageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsUniversity of Strathclyde & Medical Research Scotland
SupervisorMichele Zagnoni (Supervisor) & David Flint (Supervisor)

Cite this

'