A new method of evaluating cytotoxic drug efficacy using sub-cellular fluctuation imaging

: A pilot study of a fast and reliable method for low-throughput screening of chemical cancer treatments that could be suitable for small-scale clinical use

Abstract

This project investigated if Sub-Cellular Fluctuation Imaging (SCFI), previously and successfully used to perform rapid antimicrobial susceptibility testing in bacteria, could also be used to evaluate the effects of cytotoxic drugs in human derived cancer cells. SCFI is based on the discovery that an object inserted into an evanescent electromagnetic field generated by total internal reflection can be observed through its scattering pattern, and that sub-cellular fluctuations in prokaryotes correlate with cell viability. PC-3 (prostate), Caco-2 (colorectal), Calu-3 (lung), and A549 (lung) cell lines were used alongside two cytotoxic drugs, staurosporine and paclitaxel, or DMSO control vehicle. The results presented in this dissertation gave significant and consistent statistical differences when comparing SCFI measurements of control cells and cells treated with a cytotoxic drug known to be effective. SCFI was also able to correctly identify cytotoxic drugs against which the specific cell line is known to be resistant. Furthermore, SCFI was able to provide reliable results at 3 h after having plated the cells, making this method more than a day faster than commonly used assays. Although further research is necessary before SCFI could be applied in clinical oncology, this pilot study was able to show that SCFI possesses all the necessary qualities to be considered a viable alternative to current methods of evaluating antineoplastic efficacy.

Date of Award	24 Jun 2021
Original language	English
Awarding Institution	University of Bristol
Supervisor	Massimo Antognozzi (Supervisor) & Anne J Ridley (Supervisor)