Automated microfluidic anticancer drug screening of human tumour biopsies

This studentship is a 36-month full-time, fully-funded PhD, supported by the University of Strathclyde and AMS Biotechnology (Europe) Ltd, focusing on the automation of a microfluidic platform for screening human tumour tissue biopsies and developing in vitro immunotherapy assays.

One primary challenge in the management of all cancers is the identification of anticancer drug efficacy. Typically, a stratified or genetic-based approach is used to identify a therapy, but this often leads to severe patient side-effects or unsuccessful therapies. The ability to directly screen patient-derived biopsies prior to treatment could inform the best therapeutic strategy in a personalised manner. The use of spheroids (multicellular tumour models) for drug screening purposes provides useful tools to recapitulate drug resistance and penetration. However, the majority of these studies rely on cancer cell lines that provide too simplistic a model compared to a primary tumour. Alternatively, when human tumour tissue is used, procedures are manual and involve the use of animals into which the spheroid is engrafted (i.e. patient derived xenografts), involving high costs per screen per patient. A cost-effective, animal-free solution is provided by microfluidic technologies, facilitating combinatorial screening of tumour biopsies using miniaturised, high-throughput assays that are also amenable to developing novel immunotherapies. We have already developed a microfluidic technology for growing prostate cancer patient biopsies as cancer enriched multicellular spheroids. Our system, engineered to apply a drug concentration gradient over hundreds of biopsy-derived spheroids without the need of external instrumentation (patent pending), enables testing of 9 compounds in triplicate per biopsy, creating an unprecedented screening capability in this sector. For this technology to have impact in preclinical screening and drug development settings, scalability, ease of use and interfacing with standard biotech readout equipment must be addressed.
Within this studentship, we aim to automate and standardise a microfluidic system allowing its uptake in SME R&D labs. The experimental plan comprises three objectives:

1. Evaluation of the most throughput-effective and physiologically-relevant tissue preparation methodology that will enable spheroid formation for anticancer drug testing and immunotherapy assays.
2. Optimization of a microfluidic system for the automated time-controlled delivery of fluids.
3. Design and validate the microfluidic platform for interfacing with well-plate reader instrumentation.

Dr Zagnoni will provide expertise in microfluidics and lab-on-a-chip techniques, as well as in software development and equipment interfacing. Prof Uttamchandani is an expert in microsystem technology. Additionally, the project will benefit from a collaboration with Dr Joanne Edwards (University of Glasgow) who will provide expertise in cancer biology and drug screening and Mr Sim (AMSBIO, industrial partner) who will provide industrial and commercial perspectives in anticancer drug screening, as well as facilitating interaction with Pharma and the biotech sector.