Applications of microfluidics system for evaluating the biology of glioblastoma tissue and testing response to chemotherapy

Olubajo, Farouk Olubankole

Medicine
April 2019

Thesis or dissertation


Rights
© 2019 Farouk Olubankole Olubajo. All rights reserved. No part of this publication may be reproduced without the written permission of the copyright holder.
Abstract

The genetic and molecular variations that exist within Glioblastoma (GBM) tumours determine treatment responses. One way to improve patient outcomes is to optimise treatment(s) pre-clinically by studying each tumour on an individual basis.

Presented here are the results of an observational study on the maintenance of human GBM tissue on a microfluidic platform. The device, fabricated using photolithography processes, was composed of two layers of glass bonded together to contain a tissue chamber and a network of microchannels. A thin mesh layer was inserted to separate the tissue chamber from the microchannels and prevented blockage of the chip.

Over an 18-month period, 33 patients were recruited, and 128 tissue sections were maintained in the microfluidic device for an average of 72 hours (h). Tissue viability as measured by Annexin V and Propidium Iodide assays showed viability was 61.1 % in tissue maintained on chip after 72 h, compared with 68.9 % for fresh tissue analysed at the commencement of the experiment (P < 0.05). Other biomarkers, including LDH and Trypan Blue assays, supported the viability of the tissue maintained on chip. Histological appearances of the tissue remained unchanged during the maintenance period and immunohistochemical analysis of Ki67 and Caspase 3 also showed no statistically significant differences.

Drug testing with Temozolomide (n=6) and the experimental drug ExoPr0 (n=6) failed to show any cytotoxic effect on the tissues maintained. Preliminary analysis also failed to show any significant correlation between the tumour behaviour on chip and patient prognosis.

This work has demonstrated for the first time that human GBM tissue can be maintained ex vivo within a microfluidic device. The model has the potential to be developed as a new platform for studying the biology of brain tumours, with the long-term aim of facilitating personalised treatments.

Publisher
Hull York Medical School, The University of Hull and The University of York
Supervisor
Greenman, John (Professor of tumour immunology); Achawal, Shailendra
Qualification level
Doctoral
Qualification name
MD
Language
English
Extent
162 MB
Identifier
hull:17283
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